Neuroscience Flashcards

Question

What is Tinbergens' causation explanation of behaviour?

Answer 1

Mechanism (causation): Causal explanations in terms of what the behaviour is and how the behaviour is constructed. These explanations can include physical morphology, molecular mechanisms, other underlying biological factors, or external stimuli

Answer 2

Ontogeny (development) Developmental explanations for sequential changes across the lifespan of an individual. Often these explanations are concerned with the degree to which the behaviour can be changed through learning. Imprinting or issues of learning

Answer 3

``` Adaptive value (function) Functional explanations regarding the utility of the current form of the behaviour with regard to increasing an organism’s lifetime reproductive success ```

Answer 4

Phylogeny (evolution) Evolutionary explanations that describe the history of the behaviour, such as which ancestor first possessed this trait, what was the antecedent to this behaviour, and what selective pressures in the past have shaped this behaviour

Answer 5

``` Mutualism/reciprocity -Initiator benefit, recipient benefit Selfishness -Initiator benefit, recipient cost Altruism -Initiator cost, recipient benefit Spite -Initiator cost, recipient cost ```

Answer 6

• Your relatives are highly likely to share the same genes as you • Altruistic act for person with an altruistic gene altruistic gene will survive (therefore indirect fitness- ensuring survival of gene through self-sacrifice) • Assume there are genes for helpful behaviour (Hamilton, 1963) o An altruistic act confers a cost to the donor, but it gives a benefit to the recipient o However, if the recipient is related to the donor, then there is a chance that the genes for helpful behaviour will receive the benefit (but in another person)

Answer 7

• Whilst there is a cost to the individual carrying copies of these genes, there is an advantage to the genes in the population if: relatedness x benefit > cost o This might be if people are your kin o This might be if you live in a community with a lot of other altruistic people • Acts can appear altruistic in the short term, but if it is reciprocated later, both donor and recipient benefit in the long term

Answer 8

• This might affect: o Maternal and paternal love o Grandparent effect  Grandparents live to take care of offspring- selects for the genes of longevity o Non-breeding relatives  Might explain homosexuality: non-breeding relatives live to take care of other relatives

Answer 9

o You give something that is of low value to you to someone who values it highly o They give you something that you value highly but is of low value to them

Answer 10

o There is a low cost to donor and high benefit to recipient  Trade a surplus for a deficiency o Must have a reasonable chance of receiving reciprocation  Propinquity- need to be close to one another o Must be able to delay immediate gratification  Humans are the best at this (Fehr and Rockenbach, 2004) o Must be able to remember and punish cheaters  System works a lot better and everybody is fairer if you can identify and punish cheaters (Fehr and Rockenbach, 2004).

Answer 11

• Pot of money at start and everyone has to contribute a little bit into the common good (which is doubled and distributed equally to everyone in experiment) • People start to realise that they can get away with not giving as much to common good and then get a benefit o Everyone starts to contribute less and less so people get less money overall • Then allowed people to punish other people that don’t contribute as much as they should • Everyone suddenly started to contribute to common good

Answer 12

 Most moral codes are based around issues of fairness or following authority

Answer 13

• 2 ways in which you can get people to contribute to a common good o Individuals identify cheaters, get angry and punish them o Authority that controls behaviour of people in community

Answer 14

• People were asked to analyse the Wason selection task in two different contexts: o Describing the rules of a social contract o Being asked to detect cheating  People are much more likely to solve the Wason selection test if it is presented as a test to detect intentional cheating  Much easier to do than abstract problem o People may have modules to detect cheaters (specific for this type of problem)- built in parts of the brain specific to detecting blatant cheaters

Answer 15

• Development of intelligence o Need to have cognitive abilities to detect if someone’s cheating o To remember who they are o To maintain these relationships • The demands of the social context drives the evolution of general problem-solving abilities in order to maximise personal fitness in this context (e.g. Tooby and Cosmides, 1992) o Remembering interpersonal interactions  Expecting to get altruistic thing back if you gave  Episodic memory o Transitive inference in hierarchical power relationships o Deception  To be a good cheater, need intellectual skill o Planning o Arguing and getting your way • Became smarter because others became smarter: need to get smarter than cheaters

Answer 16

• Cohesive social groups provide overall advantages to fitness to the members of the group

Answer 17

• Frans De Waal o Monkey gives rock to experimenter to get reward o When monkeys treated unfairly:  If give one grapes and one cucumber, create unfair situation  If monkey sees the other getting grapes, will refuse piece of cucumber given and will react poorly and refuse to eat the cucumber piece • Human morals and ethics have evolved o Biological basis in sense of fairness and ethics because sense is present to some degree in monkeys • Biological basis to maintain fairness, equity and fair trade

Answer 18

``` o Aggression  Within communities/groups  Between communities/groups  Within sexes  Between sexes o Inequality  People are in the situation they’re in because of an innate quality: not because of social unfairness o Social Darwinism o Eugenics • Most people concentrate on the idea of competition driving evolution ```

Answer 19

• Many ways to increase fitness o Accidental adaptations o Sexual selection o Inclusive fitness and reciprocity

Answer 20

• Sexual selection- depends on the advantage which certain individuals have over others of the same sex and species, in exclusive relation to reproduction, sometimes resulting in adaptations which are detrimental to survival itself. Two component processes: o Same-sex competition (intrasexual competition)  To gain preferential access to mates through competition of the same sex  Mostly done by males o Mate preferences (intersexual competition)  One gender might prefer specific features of the other sex  Mostly done by females • A special case of natural selection-most important thing in evolutionary fitness o Competition within a sex for mates o The choice of with whom to mate o Selection of a partner who will maximise the fitness of the offspring through:  Conferring healthy traits to offspring  Parental investment

Answer 21

• Selection pressure on traits that reliably signal health and/or parental investment o Physical traits signalling health, determining attractiveness o Behavioural traits, signalling competitiveness and parental investment

Answer 22

• Attractiveness almost entirely determined by culture and time o Fashion amplifies and exaggerates type of features

Answer 23

o Facial symmetry-prefer symmetry (both men and women)  Linked with health advantages- better immune system o Hip-waist ratio of about 0.6-0.65 for women, as well as fat on hips, breasts and buttocks  Linked with lower risk of cardiovascular diseases: signal for fitness and signal for nonpregnancy (Welborn, Dhaliwal and Bennett (2003)) o Shoulder-hip ratio for men  Signifies strength and athletic ability o Clear skin o Lustrous hair o Full lips o Good muscle tone

Answer 24

o Theory of Reciprocal Altruism o Theory of Parental Investment and Sexual Selection o Theory of Parent-Offspring Conflict

Answer 25

* Hypothesis 1: In species where the sexes differ in parental investment, the higher investing sex will be more selective in choice of mating partners * Hypothesis 2: Where males can and sometimes do contribute resources to offspring, females will select mates in part based on their ability and willingness to contribute resources * Hypothesis 3: The sex that invests less parentally in offspring will be more competitive with each other for mating access to the high investing sex

Answer 26

 Prediction 1- Women have evolved preferences for men who are high in status  Prediction 2- Women have evolved preference for men who show cues indicating a willingness to invest in them and their offspring  Prediction 3- Women will divorce men who fail to contribute expected resources, or who divert those resources to other women and their children

Answer 27

• Some behaviours act to increase fitness of the individual o Aggression o Adaptability and behavioural flexibility • Some behaviours act to increase the fitness of the next generation o Maternal love o Jealousy • Some behaviours act as reliable signals of fitness o Music and dancing • Some behaviours increase collective fitness o Reciprocity o Memory, self-control

Answer 28

• To some extent, our mental abilities are determined by our biology • All animals have evolved from common ancestors • There should be preserved similarities between nervous systems • But there should also be evolved differences o Difference in nervous system may make differences • Therefore, compare and contrast animals to make inferences about the relationship between CNS structure and function of cognition

Answer 29

• Intelligence and problem-solving important determinants of fitness due to adaptability • Strong selection pressure for intelligence in animals • But how do you measure intelligence o Gave various types of animals simple operant task to learn and saw how long it took them to solve it  But bees turned out to be much more adaptable than a human baby • But would you get a human baby to solve the same problem as a bee? • Species specific difference in ability to do things  Process not indicative of intelligence, but indicative of ability to do the specific task o Gave various types of animals one task then another which is structurally similar but involves different types of things  Learning set- ability to transfer learning from a task to a new task which is similar  Start to see types of patterns of results that you’d expect • Based on ability to transfer learning

Answer 30

o Comparative psychologists have wanted to understand evolution and nature of general intellectual capacity by exploring performance of non-human vertebrates in a variety of learning tasks, in the expectation of demonstrating superior intelligence in species more closely related to man o It has however proved difficult to establish that any observed difference in performance is due to a difference in intellectual capacity rather than to a difference in contextual variables like perception or motivation o Basically, is difference that we’re seeing because of intelligence, or some other factor based on the test which has nothing to do with intelligence or cognition?

Answer 31

• Null hypothesis basis of problem of intelligence testing between people o Difference seen in performance because of intelligence ability or difference in ability to do the test?

Answer 32

o Put bowl of food in front of dogs o Some dogs chained up so couldn’t get to bowls of food, and the other dogs were loose (and ate the bowls of food) o Owners did not know if the dog had eaten bowl of food or not  Two rooms: • One where dog ate the bowl of food • The other where it didn’t o Would scold the dog for eating bowl of food whether or not it has eaten bowl: dog would do ‘guilty look’ whether or not they had eaten bowl of food o Guilty look not because did something wrong: instead submissive look in the face of anger o Therefore ability to look at an animal and infer its mental state not very accurate: can misinterpret behaviour

Answer 33

• To what extent is complex human-like behaviour simply the result of simple learning processes? o Spontaneous problem solving vs learning, discrimination and generalisation o A problem of inference  Inferring a mental state from behaviour • To what extent is human problem solving any different? o Complexity from simple processes

Answer 34

* In no case may we interpret an action as the outcome of the exercise of a higher psychical faculty, if it can be interpreted as the outcome of the exercise of one which stands lower in the psychological scale * The canon doesn’t exclude the interpretation of a particular activity in terms of the higher processes, if we already have independent evidence of the occurrence of these higher processes in the animal under observation * If you can explain a behaviour through a simple process then don’t need a higher more complicated process for that sort of thinking

Answer 35

Thorndike (1911) • No such thing as insight in animal kingdom, but simple and dumb learning processes that produce apparently intelligent behaviour

Answer 36

• Behaviour cannot be reduced or explained by reducing it to simple mental processes- have to explain behaviour in terms of combined mental processes o The sum of parts is different than its whole • Kohler wanted to see if chimpanzees would get bananas suspended up in the air: solution dependent on environment around them and the chimpanzee • Sultan experiment o Tried to see if chimpanzees understood tool use and how to use it o Put chimpanzee in cage with short stick with food out of reach of chimpanzee and short stick + chimpanzee but within reach of long stick + chimpanzee, as well as a large stick in separate cage that was out of reach of chimpanzee but within reach of short stick + chimpanzee o Found that chimpanzee solves the puzzle (had sudden insight into whole of problem when eyes on solution) with knowledge of tools used in the past

Answer 37

* Replicated Kohler’s banana in the air experiment * Trained pigeon not to fly * Shaped pigeon so that if it pecked banana, it got rewarded * Then put block on floor with target and if pigeon pushed block over to target point, then got a reward * Training behaviour independent, wanted to see if pigeon would combine the together to get both rewards * Epstein argued that Kohler’s experiment worked because chimps had already played with tools, not because of sudden insight- and sum of parts were the whole because they had the parts together

Answer 38

* Tube with worms for bird at the bottom * Bird given a straight piece of wire and has to figure out how to get basket out with worms using wire * Crow made curved wire to solve problem despite no previous experience with puzzle, but had had experience with curved wires * She did not show insight or purposeful tool manufacture due to the fact that in each first trial, she tried first with the straight wire without bending it, but did show evidence of reinforcement history

Answer 39

• Intelligent behaviour in animals doesn’t arise spontaneously, but occurs with practice (some element of reinforcement but above instrumental learning) • Use of tools only occurs if o Opportunity to play o Watch others • But the use of the tools is entirely novel for each situation and is not a repetition of past (reinforced) behaviour

Answer 40

* Can chimpanzees plan for the future * Learnt to get rocks and throw rocks at people and liked to watch people run when he threw the rocks * Removed the rocks yet he kept finding more rocks * Through video surveillance, found that at night, was breaking pieces of concrete and storing them into hidden stash * Future planning- making tool for future use

Answer 41

• Have to have some idea as your body as yourself

Answer 42

• Put mirror in dolphin tank • Get dolphin to come up and swim to the trainer in the tank • The trainer will put a visible mark on the dolphin in an area that is hard to see, or just pretend to put a mark (to see if the dolphin, when it had a mark, was just checking itself out because of perceptual capture ) • Dolphin will look at mark, or try to find mark, on themselves • Also passed by: o Humans o Primates ----Initially not recognise themselves but will recognise themselves after a bit ----Use the mirror to look at bits of itself -to reference and observe themselves o Elephants • Theory of own self- first step in theory of mind

Answer 43

• A person intends to do something • Need to find what the goal of that behaviour may be • To do help, need to understand that the person needs help and what it wants • Warneken, Tomasello o Altruism in children and chimpanzees  Prosocial behaviour in children- requires understanding of what the person needs and wants by looking at person’s behaviours  Prosocial behaviour in young chimps as well- chimp helped person pick up sponge (with no verbal cues)

Answer 44

* Another individual wants/believes something different than the self * Human theory of mind is closely tied to language • Nonverbal false belief task- Call and Tomasello o Performance of children and great apes  Person 1 hides banana in a box and leaves the room (doesn’t know that banana has been switched), another person switches the banana in another box. Asked to indicate where person 1 will think the banana is  In children, kicks in at 5 years old (whether verbal or non-verbal) • Autism- fail false belief but pass true belief and control task • Specific language impairment- completely fine with every task  In great apes, pass the false-belief test

Answer 45

* Need theory of mind for reciprocal altruism and reciprocal trade (where can figure out what other individual needs) * Need theory of mind for deception and cheating- can see what people know and exploit what the other person does not know

Answer 46

• Continuity between species o Comparative psychology  Allows us different perspectives on intelligence that only studying people doesn’t allow us to do • Variation of intelligence seen in people is extremely small • Instinctive behaviours o Major influence on James, Freud and ethology • Developmental theory o Progress through stages of development • Morals o Adaptive significance of behaviour rather than theological doctrine • Individual differences o Study of the variation between individuals

Answer 47

• Genes are locations on chromosomes o Basic unit of heredity o Encode functional RNA and proteins o Transmission of genes to offspring is the basic process of inheritance  Chromosomes replicated in germ cells and passed on to next generation o Locations on chromosomes are certain genes important for certain characteristics

Answer 48

• Genes can vary between and within people | o Genes in same location, but version of gene may be different from person to person

Answer 49

o Homozygous-one version of gene on both chromosomes

Answer 50

o Heterozygous- one chromosome has one gene, the other has other gene version  If one dominant over the other, phenotype will express dominant gene

Answer 51

• Heritability is the component of the variance of the phenotype that can be explained by heritable factors o Heritability increases when genetics are contributing more variation or because non-genetic factors are contributing less variation: what matters is the relative contribution o Heritability is specific to a particular population in a particular environment o Heritability of a trait should not be interpreted as a measure of the extent to which said trait is genetically determined in an individual o Assumes no epigenetic interference • Heritability quotient- H^2 o H^2= V(g)/V(p)

Answer 52

o Identical-monozygotic twins |  Come from same sperm and egg and shared placenta, which then splits into 2 individuals

Answer 53

o Fraternal- different to each other -dizygotic twins  Two separate sperms and eggs at time of fertilisation  Separate placentas- two different individuals born at the same time

Answer 54

• Test heritability through twin studies • Heritably estimates done by looking at similarity of traits between these types of twins • Calculate the correlation between siblings on some phenotype o Monozygotic twins raised together o Dizygotic twins raised together o Monozygotic twins raised apart o Adopted siblings • Differences in these correlations can be used to estimate V(g) and V(e)

Answer 55

• It is assumed that P=A+C+E=1 o A-variance from additive genetic components o C-variance from a common family environment o E-variance from a unique personal environment • Correlation of monozygotic twins=A+C=1-E • Correlation of dizygotic twins=0.5A+C • Correlation between monozygotic twins raised apart=A • Correlation of adopted siblings=C

Answer 56

• Bouchard et.al o Studied mental and physical traits of identical twins reared together as well as dizygotic twins reared apart to assess the relative contributions of genetic and environmental factors on the physical, mental and personality traits that creates human individuality o Found different of ratios of similarities between the twins o Correlation (monozygotic twins reared apart)/correlation (monozygotic twins reared together)= A/(A+C)  Physical traits- very similar, mental traits- there is strong genetic component and environmental contribution o Bouchard estimated the heritability of a personality to be about 40% o Bouchard estimated the heritability of intelligence to be around 70% o But because individuals are likely to seek outlets for their innate tendencies regardless of what environment they are reared in, one will never be able t provide a definite or undisputed estimate of heritability for any given trait

Answer 57

• Measurable expression of a trait is the phenotype | o Phenotype- physical measurement that trait

Answer 58

• Phenotypic variance (Vp) = Vg +Ve+ Vge o Vg- genetic variance  Additive components (Va) + dominance components (Vd) + gene interaction effects (epistasis-some genes modulate expression of other genes) (Vi) o Ve- environmental variance  Common environmental (Vc)+ unique environment (Ve) o Vge- gene-environment interactions

Answer 59

• Studying ‘genetic architecture’ o Characterise quantitatively a behavioural phenotype in a given population/strand derived from nature or by artificial selection o Examine the changes in phenotype in sets of progeny from test crosses between different populations o Infer statistically the number of genes responsible and their interactions o Look at entire genome of individuals code sequence of individual and look to see if there are variations of phenotype relations with that of the entire gene

Answer 60

• Tryon (1940)-continuation o Wanted to see if there was a single gene responsible for intelligence o Got dull rats and bright rats and bred them together(F1) o Got animals from (F1) and bred them together o Bright strain and dull strain did not reemerge- therefore brightness and dullness not a single gene and is a polygenetic trait (associated with many genes)

Answer 61

• Quantitative trait loci are mapped by identifying which molecules markers (such as SNPs) correlate with an observed trait • Then sequence the actual gene that cause the trait variation • We can identify sections of the chromosome that are linked to the trait statistically: o We know the locations of some variable ‘markers’ on the chromosomes o We can calculate whether the changes in the expression of a trait is linked with polymorphisms at these sections of the DNA  Single nucleotide polymorphisms • Some specific nucleotide positions in a species’ genome are highly variable • By mapping the sequence of DNA in many individuals, the locations of high inter-individual variance can be mapped across the genome • This variance can then be correlated with variance in a trait  Can make a manhattan plot- probability that variation in that part of the genome correlates with variation of a trait • Then check is specific genes in that region are driving variation

Answer 62

* Studying the contribution of likely candidates for a phenotype based on what is known about their neurobiological bases- what sort of biological mechanisms that could underly a trait * Got sample and scanned the genome  see what gene is there psychological tests to determine prediction of performance in specific task

Answer 63

o Alcohol dehydrogenase as a marker for alcoholism

Answer 64

 Goldberg and Weinberg o Tested difference in working memory  Found association between COMT polymorphisms and prefrontally-based executive functions and neurophysiology

Answer 65

o Catecholamine-O-Methyltransferase (COMT), enzyme that helps break down neurotransmitters as a marker for cognition • There are two different types of COMT gene- o High activity and thermostable- Valine amino acid variant o Low activity and thermolabile- Methionine amino acid variant

Answer 66

• Techniques o Testing people with polymorphisms of the gene o Genetically modified animals

Answer 67

 Mice-genome manipulated so that leptin has been disrupted so that animal has no longer produced it • Mouse that has lost leptin gene has lost ability to stop eating • Leptin is important for its regulation of appetite  Easily done with CRISPR- which inserts new genes in animals to see if it produces change of behaviour

Answer 68

• Twins as representative of the population o Are twins treated differently or similarly as other kids? Are they appropriate as a population sample? • Contextual nature of the results o Very had to replicate results from lab to lab or using different measures of the same trait o Laboratory specific effect-suggests estimate types are not very precise • Mis-estimation of differences in V(g) and V(e) o Miss out dominance and interaction effects (ignoring these genetic contributions), therefore may overestimate A o Monozygotic twins raised apart- assumed that the variation between these is only determined by their genetic component but could be an underestimation of a common environment for these twins (kC) • No estimation of V(ge)

Answer 69

• Case study: Jack Yufe, Oskar Stohr o Born in Jamaica o Oscar was taken to Germany and put into the Hitler youth (catholic) whilst Jack was brought up Jewish o When came together for Minnesota twin study, they hated each other because of huge variation in political views but noticed they had a lot of similarities  Breaking tension in room by sneezing

Answer 70

• Ignores the important contribution of background genotype to phenotype o Effects of genetic manipulation might vary from strain to strain o Effects of a gene might depend on other genes being present of absent (epistasis) • Redundancy and pleiotropy in mechanisms obscure the ability to draw relations between genes and traits • Ignores roles for adaptation and developmental effects o The apparent changes in phenotype might not be due to the direct effect of the gene, but due to compensatory changes during development  Animal as it develops adapts to the fact that it doesn’t have that gene- gene changes developmental trajectory in a way that is unpredictable • CRISPR twins- Modification China o Used CRISPR to delete CCR5 receptor for girl to prevent her from catching HIV o Girl has altered psychological profile due to downstream effects

Answer 71

o Redundancy- more than one gene produces the same effect, so knocking out a gene might have no visible effect on a trait  Lots of redundancy in biological systems

Answer 72

o Pleiotropy- a single gene might contribute to more than one trait

Answer 73

• Results do not identify individual genes: o Necessity for discovering candidate genes at the sections of DNA that are highly associated with the trait o Follows the effects of multiple genes with small contributions to phenotypes • Necessity for large pedigrees and cross-mating makes human studies unlikely o Except Iceland pedigree • Need large samples -High risk of false positives

Answer 74

• Lack of evidence for any complex psychological trait that is determined by a single gene o Also a lack of consistency between polygenic studies  Different sets of data can express different things • What does a genetic marker actually mean o Is it predictive or useful, or is it just a basis for discrimination • Vagueness in incorporating a mechanistic role for the gene in the phenotype • Often a definitional or measurement problem with psychological traits o Measurements are poorly verified • Behavioural phenotypes tend to be more polygenic than other traits

Answer 75

• A gene o Makes other genes (replication during cellular division) o Makes RNA (transcription) o Part of DNA sequence (with promoter and enhancer) which produces pre-mRNA which gets edited (by splicing and other stuff) into mRNA which gets translated into a protein

Answer 76

• RNA o Can be used to regulate genes (go back into nucleus and regulate other genes) o Can have enzymatic activity (RNA based enzymes) o Can make protein (translation)

Answer 77

• Proteins o Regulate genes (go back into nucleus) o Have enzymatic activity o Have a structural role (can form cytoskeletons) o Are used in signalling (released within organelles in cell or go to other cells)

Answer 78

1. Regulate at the level of transcription  Determine whether or not gene is read into mRNA 2. Regulate at level of translation  Determine whether or not mRNA translated into a protein 3. Post translation control  Regulation of protein activity • Post translational modification of proteins can change their structure and hence function • Change their efficiency levels 4. Natural selection of genotype

Answer 79

• Gene expression: | o Measure mRNA (PCR, in situ hybridisation)

Answer 80

• Protein translation | o Measures concentration of proteins (ELISA, Western blot, etc)

Answer 81

• Post-translational modification | o Measuring protein variants and isoforms (ELISA, Western Blot, …)

Answer 82

• Can build map in brain/body as to whether or not there is a gene and whether this gene is active or not (dynamic activity) in an individual at different epochs in person’s life

Answer 83

``` • Epigenetic mechanisms are affected by these factors and processes: o Development o Environmental chemicals o Drugs/pharmaceuticals o Aging o Diet ```

Answer 84

• DNA methylation | o Methyl groups (an epigenetic factor found in some dietary sources) can tag DNA and repress genes

Answer 85

o To read off gene bound to histone, have to slightly unwind genes (needs to be a little bit of looseness) o The binding of epigenetic factors (can be acetylated) to histone tails alters the extent to which DNA is wrapped around histones and the availability of genes in the DNA to be activated o Acetylation makes it easier to read, methylation makes gene harder to read

Answer 86

o Histones are proteins around which DNA can wind for compaction and gene regulation

Answer 87

• Crabbe et al. o Range of mice different strains raised in different labs and set up 3 different labs in US o Trained them how to run behavioural tests- tried to get everything reliable and consistent in the different o Mice- open arena-give mice substance- try to see how much they move around arena o Different results based on where the tests were run o Subtle effects that are hard to control against that produce changes in behaviour for genetically similar animals (environmental effects)

Answer 88

1. Genetic and environmental effects might be independent but additive a. Phenotypic variation =A+C+E 2. Some environmental effects might only be seen under certain genetic conditions 3. Some genetic effects might only be seen under certain environments a. An individual may have a genetic predisposition to antisocial behaviour, but not demonstrate this trait unless he or she experiences abuse or neglect in childhood b. A genetic predisposition may be overcome by protective environmental circumstances i. For example, individuals with a predisposing to alcohol abuse may live in a culture that forbids the consumption of alcohol 4. Some genetic effects might influence the environment to which an individual is exposed a. Alcoholics tend to create an environment that facilitates drinking i. Alcoholics tend to self-associate with other alcoholics ii. They have a lot of alcohol in the house iii. Importantly, children of alcoholics tend to grow up in environments rich in alcohol, increasing their chances of being exposed to alcohol b. Create a risky environment for themselves and their genetic predispositions are shown

Answer 89

a. Cooper and Zubek-1958 i. Got Tryon’s bright and dull rats to see if environment affected them ii. Raised rats in enriched environmental conditions and restricted environmental conditions 1. Normal environment: 4-8 mice, large tubs, little colony 2. Enriched environment: Large enclosure, running wheels, social colonies, ropes to climb… 3. Restricted environment: social isolation iii. Bright strain of rats in enriched environment didn’t show any benefit but dull strain of rats did (genetic background of rats determined whether enriched environment had any effects) 1. Saturation effect for bright rats iv. When restrict environment, didn’t do much to dull strain of rats but stunted growth of bright rats (genetic background of rats determined whether restricted environment had any effects)

Answer 90

i. People carry different versions of this gene: 1. Alleles are ε2, ε3 and ε4 ii. People who contract Alzheimer’s disease at a younger age are far more likely to carry the ε4 allele than is normal in the population 1. Relative risk iii. Women taking estrogen (hormone therapy) to minimise AD diagnosis are benefited only if they don’t have ε4 iv. Head injury isn’t linked to AD unless there’s also ε4 v. Genetic link between the effect of environment to development of cognitive aspect

Answer 91

• Came from cancer biology o Found that DNA that suppressed tumors was chemically modified (methylated) in cells that were cancerous compared to those who weren’t

Answer 92

• Under condition of food stress, serotonin production changes in nervous system of grasshoppers so that genes get modified, which has hormonal effect which changes grasshopper colouration and encourages aggressive behaviour. They become locusts. o Locusts and grasshoppers same species- one is just of different genetic activity to the other

Answer 93

• Epigenetics refers to the changes to the functional genotype of the cell o DNA code is not altered but chemically modified so transcribed and translated in different ways then before  It is chemically modified so that some parts of it become less (or more) likely to be expressed o This can produce long-lasting and even permanent changes in the phenotype • Epigenetic switches and markers (which are chemicals on DNA) can help switch on or off the expression of particular genes • Epigenetic signals from the environment can be passed on from one generation to the next • Bidirectional Manners of epigenetic regulation o Physically blocks access to genes by altering histones (winding them more tightly/ unwinding them) o DNA methylation- involves the addition of a methyl group to particular bases in the DNA sequence

Answer 94

* Nazis occupied the Netherlands- as allies pushed them out, destroyed all ports and bridges in Holland * After, winter followed: people who lived near river and coastline could get food delivered to them but couldn’t bring it to interior because of lack of bridges * Huge famine resulted-a lot of children starved * Found that children in the interior of the Netherlands tended to develop mental health disorders as they got older compared to people who lived near the rivers * Children in interior have higher levels of methylation on particular genes compared to those who lived on the coast

Answer 95

• One twin was sent to space for 365 days, the other stayed on the ground • NASA got the two to go through pre-flight test, during flight and postflight to test markers o Biochemical o Cognitive o Epigenomics o Gene expression o Immune o Metabolomics o Microbiome o Proteomics o Physiology o Telomeres • Twin that was up in air showed changes to epigenetic markers and changes to cognitive markers postflight o Showed massive change in ability to do processing speed tests and attentional tests

Answer 96

• Problems with trying to find ‘genes for a behaviour’ o The genetic contribution to a behaviour might be indirect o It’s not necessarily the type of genes you hold that’s important (the genotype), it’s whether the genes are expressed (the functional genotype) o The functional genotype is heavily affected by environment • Inherited variations in phenotypes are heavily determined by subtle variations in common environments that are stable across generations

Answer 97

* Genes rarely program behaviour * They might provide a disposition to behave * This disposition can then be reinforced or eliminated by the environment across development * So while there may be a genetic component to behaviour, it requires an enabling environment to be expressed * Expression of behaviour is influenced by culture- have fundamental need but expression is expressed through different types of cultures * Behaviour itself can be quite flexible but what is occurring at the biological level might be fundamental to the simple motivational and emotional processes that motivate the type of learning that you have from your culture

Answer 98

o Maternal behaviour of rats  Protect their pups in specific kind of way • Arched back nursing o Presenting their tits to the pups to allow them to drink • If pups get distressed, the mum licks and grooms o High licking/grooming mums (H) vs low licking/grooming mums (L)  Adopt out all the offspring of H and L mums at brith  Give half of each group to H or L mums  Gives 4 groups • H-H, H-L, L-H, L-L  And undisturbed (C ) or disturbed (w) controls • H/C, L/C, H/w, L/w o Is maternity heritable? o Examine three things  What is the rate of licking or grooming of the L or H mums to their adopted or natural offspring?  Do the offspring show changes in tests of anxiety as adults?  Do the offspring change the type of maternal care they show their own offspring when they breed o Those who had high maternal care mums and were raised in high maternal care families also displayed high maternal care to their pups o Those who had low maternal care mums and were raised in low maternal care families also displayed low maternal care to their pups o Those who had high maternal care mums and were raised in a low maternal care environment gave low maternal care to their pups o Those who had low maternal care mums and were raised in high maternal care environment gave high maternal care to their pups

Answer 99

 Rats raised by H mums are less anxious when adults • Found by placing pup adults in an open environment  What happening when young changed emotional responses for rest of life • But not a genetic thing- imprinted by environment

Answer 100

 Wanted to see what was happening in the brain of these adults • Got those who came from high maternal care mums which were given no extra care with stroking paintbrushes • Got those who came from high maternal care mums who were given extra care with stroking paintbrushes • Got those who came from low maternal care mums who were given no extra care with stroking handbrushes • Got those who came from low maternal care mums who were given extra care with stroking handbrushes  Did this through in situ hybridisation • High levels of glucocorticoid in high maternal care pups (functioning stress response) • Low levels of glucocorticoid in low maternal care pups (non-functioning stress response) • Extra handling with brushes equalised differences between high and low maternal pups • Those who were given care when they were young had low CRH as adults • Those who were not (so the low, no extra handling group) had high levels of CRH as adults  Nothing to do with genes animals hold- all about functional expression of genes that they had that is important- environment alters this functional expression  Found that low maternal care resulted in tightly bound DNA to histones- high DNA methylation of genes in brain important for glucocorticoid receptors and other stress related gene systems  Found that high maternal care resulted in loosely bound DNA-histones had high levels of acetylation in stress genes

Answer 101

 Behaviourally inheritable trait- maternal care • An animal behaves similarly to mother it is looked after by (cultural transmission) • Not social learning that’s doing this  This behaviour is inducing an emotional change in the pups- different levels of childhood stress  Emotional change in pups substantiating itself into biology of brain through epigenetic changes to stress axis  Genetic change is maintained for natural life of individuals such that it changes their emotional responses in life- poor regulation of stress and anxiety for low maternal  This emotional expression influences the maternal care that they give later in life an adult o It’s not the epigenetic regulation of “genes for maternal behaviour.”. It is an indirect effect via emotional regulation Summary: • The indirect effect on maternal behaviour: o Not an environmental effect on genes for maternal behaviour o Effect is on genes important for emotional regulation o Poor emotional regulation then spreads to negatively affect other behaviours, including maternal care

Answer 102

• CRH is made in nerves in the hypothalamus and is released into the pituitary CRM/CRF= corticotropin releasing hormone/factor • ACTH is released into bloodstream from the pituitary o ACTH= adrenocorticotropic hormone • Glucocorticoids are released from the adrenals o Glucocorticoid= cortisol in humans, corticosteroid in lab rats • Glucocorticoids have many effects on physiology and CNS to increase capacity to cope with stressors • Loop is under control of glucocorticoid receptors in cortex, hippocampus and hypothalamus: these inhibit the release of CRH

Answer 103

• This is one of the reasons why it’s so hard to see clear links between genes and behaviours o Variations in a behavioural phenotype might be due to variations in genetic activity of genes important for other factors (e.g. underlying emotional, motivational, cognitive factors) o Variations in these factors might be heavily influenced by environmental context • This is why it’s important to understand the psychological factors that contribute to behavioural phenotypes

Answer 104

``` • Neuron has: o Cell body o Dendrites feeding into the cell body o One long axon covered in myelin or oligodendrocyte sheaths o Synapse-Space between the two neurons ```

Answer 105

o Neurons are discrete cells o Information/action potentials in a neuron travels in one direction (from cell body down to synapse) o Synapse occurrence triggers postsynaptic neuron to form its own action potential

Answer 106

• First part o Dissected out a rabbit heart and left intact the vagus nerve from the base of the brain onto the heart of the rabbit and put it into the solution o If had correct nutrients in the bath that the heart was in the heart would continue to beat after taken out of rabbit o If stimulated vagus nerve with electricity, could change rate of heartbeat  Electrical stimulation of vagus nerve which regulated cardiovascular activity in the rabbit

Answer 107

• Second part o Placed second dissected heart in a different vessel that was connected by a fluid bridge to the original vessel with the first heart o Showed that if stimulated the vagus nerve and changed cardio activity of heart A, after a period of time, would also change activity of heart B o Showed that stimulation of vagus nerve produced excretion of water soluble factor which then changed the activity of the cardiac muscle o Not electrical stimulation directly causing the effect of the nervous stimulation of the cardiac muscle, but the release of some soluble chemical factor driving this effect

Answer 108

o Vesicles with neurotransmitters come down from the nucleus along microtubules to the presynaptic mass  They will then remain inactive o An action potential will hit the synapse o When this occurs, voltage change of the membrane caused by the action potential causes some transmembrane channels to open which are specific to calcium ions o Calcium ions rush into the neuron which changes configurations of proteins surrounding the vesicles, making them stick to the intracellular presynaptic membrane o Once stuck, proteins on extracellular presynaptic membrane causes vesicle to open o Neurotransmitters in the vesicle are released into the synapse o Once neurotransmitters released into the synapse, receptors on postsynaptic neuron mass are sticky to the neurotransmitters and bind to the neurotransmitters o When receptors bind to neurotransmitters, they change the electrical gradient in post-synaptic membrane  More negative-makes it less likely for post-synaptic neuron to fire  Less negative- makes less negative, which makes it approach the firing threshold for the action potential o Electrical  chemical  electrical system o More points of control around ability for variable changes

Answer 109

Cholines - Primary neurotransmitter from muscular nerves to muscles - Also in CNS Monoamines - Catecholamines - Indolamines Amino acids - Primary neurotransmitter in CNS/ the most abundant - -Excitatory - -Inhibitory Peptides -Opioids Lipids -Endocannabinoids Nucleosides -Purines

Answer 110

Acetylcholine Ach

Answer 111

Nicotinic, muscarinic

Answer 112

- Dopamine DA (main neurotransmitter released in the reward circuit) - Norepinephrine/Noradrenalin NA (same compound)

Answer 113

Serotonin 5HT

Answer 114

Alpha and beta adrenergic

Answer 115

14 types of 5HT receptors

Answer 116

Glutamate or Aspartate | -Glutamate is the most widespread excitatory neurotransmitter

Answer 117

GABA | -GABA is the most widespread inhibitory neurotransmitter

Answer 118

NMDA (important for learning and memory) and kainite. AMPA and mGlu are the main ones in terms of nervous activity

Answer 119

GABA-A, GABA-B

Answer 120

Endorphins

Answer 121

Anandamide

Answer 122

Cannabinoid

Answer 123

Adenosine, Purinergic

Answer 124

• Many neurotransmitters are generated in discrete nuclei that may project widely through the brain o In every nucleus within the brain there are interneurons which generally release excitatory or inhibitory amino acids

Answer 125

• For monoamines, only have a few places which release these types of neurotransmitters o Only 2 nuclei make neurons that produce dopamine  Substantia nigra which projects into the striatal system  Ventral tegmental area projects into multiple parts of the brain important for emotional processing, and into the cortex o Noradrenaline  Only one part of the brain generates neurons which produce noradrenaline  From this point, spread out around brain and release noradrenaline in various parts of the brain for various functions o Serotonin  3 main nuclei which produce serotonin neurons but they spread all throughout nervous system to regulate activity of different nuclei in the brain

Answer 126

• Drugs bind to a receptor to generate a biological response

Answer 127

o Binding is usually transient- the drug (ligand) sits in the binding domain for various periods of time (determined by strength of affinity-demonstrated by k coefficient) and dynamically binds through stochastic random process until the drug is metabolised  Will form a complex so that when receptor binds the drug some change in the shape of the receptor occurs such that intracellular tail of receptor produces some biological effect

Answer 128

- Ionotropic | - Metabotropic

Answer 129

 Common type in the brain  Binding of neurotransmitter to receptor opens an ion channel which produces immediate change in the electrical potential of the neuron membrane  Immediate and rapid changes to neuronal activity

Answer 130

• E.g. GABA- 4 subunits produce an ion channel which cross receptor membrane o When receptor bound to channel, channel became open and opened to a degree which allows chlorine to come through from intracellular to extracellular space o Makes interior of neuron more negative  More negative a neuron is, the harder it is for the neuron to generate an action potential which is why GABA is inhibitory • Sodium ions can also come through some excitatory ion channel receptors to make the neuron more positive and hence encourage action potentials

Answer 131

 Type I: • Molecule of transmitter substance binds with receptor • Receptor activates G protein • Alpha subunit of G protein breaks away, binds with ion channel and opens it • Ions enter cell, produces postsynaptic potential

Answer 132

 Type II • Molecule of transmitter substance binds with receptor • Receptor activates G protein • Alpha subunit of G protein breaks away, activates enzyme which produces second messenger o The involvement of second messenger systems allows better integration of neural signals and more variation in how the cell might respond • Ion channel opens • Ions enter cell, produce postsynaptic potential

Answer 133

 Because of the extra steps, these receptors have slower action

Answer 134

• The effects can be: o Changing the post-synaptic membrane potential  Hyperpolarisation= less likely to fire  Depolarisation= more likely to fire o Activating internal signals that can  Change gene expression and potentially the phenotype of the neuron  Increase the number of receptors on the surface making it more/less sensitive  Modify the activity of other metabotropic receptors

Answer 135

• Neurotransmitters release and activity in the synapse is tightly regulated so that quicker pulses are transmitted from one neuron to another (signal sharp and quick so can have it more frequently)

Answer 136

• When they leave the postsynaptic receptor and go back into synapse after having done their job, they are taken back up by the presynaptic neuron by transporter proteins. They are then either: o Re-packaged into vesicles for more use o Destroyed by enzymes in the presynaptic neuron

Answer 137

drug which mimics a neurotransmitter spatial shape and results in corresponding change in resting potential

Answer 138

drug which blocks a neurotransmitter at its receptor hence making sure that that receptor is not available for binding for natural neurotransmitter • Antagonist still fits in receptor but shape is slightly different than required for signal production so just blocks the receptor

Answer 139

o Enhancing release of neurotransmitter (L-Dopa enhances the production of dopamine) o Binding directly to receptor  E.g. THC, Benzodiazepene, Heroin, Nicotine and Ethanol o Blocking reuptake of neurotransmitter by blocking transporter proteins or reversing transporters so that they actually cause the release of neurotransmitters  E.g. MDMA, antidepressants, Cocaine, amphetamines  Some drugs reverse these transporters o Blocking enzymes that destroy excess neurotransmitters  Catecholamines, MAOA (anti-depressant drugs which target serotonin and noradrenalin) and MAOB (which targets dopamine)

Answer 140

o Blocking receptors |  E.g. Naloxone, ketamine, anti-psychotics

Answer 141

o Selective serotonin reuptake inhibitors  Fluoxetine blocks reuptake of serotonin because they antagonise serotonin specific transporters in the presynaptic neuron o Serotonin and norepinephrine reuptake inhibitors  Venlafaxine o Tricyclic antidepressants  Work on reuptake/transporter o Monoamine oxidase inhibitors stop degradation of neurotransmitters so increase supply of neurotransmitters

Answer 142

• Earliest anti-depressants were discovered by accident o Iproniazid was originally used for tuberculosis but researchers noticed that patients experienced a relief of their depression o Was then discovered to inhibit Monoamine oxidase (an enzyme that breaks down monoamines such as noradrenaline, dopamine and serotonin) and elevate serotonin o Reserpine was an anti-hypertensive that depleted monoamines and caused depression

Answer 143

• Newer MOAs were developed but they are still associated with severe side effects o Were effective for some types of depression but had severe side effects, one of these being tyramine-derived symptoms • Side product of tyramine is severe in people and MOA inhibitors break down tyramine naturally • Compounds can accumulate in body and become toxic

Answer 144

All later effective drugs were designed to increase synaptic monoamines o Tricyclic antidepressants block reuptake pump, which consequently leaves more neurotransmitter in the synapse o Selective serotonergic reuptake inhibitors have been developed to block reuptake of serotonin alone. o This lead to the idea that depression may be related to insufficient cortical or limbic monoamines, NA, DA, 5HT o But:  There’s a therapeutic lag in the action of anti-depressant drugs (need to be given for 3 weeks) • Monoamines increase immediately after starting the therapy, but the therapeutic effects can take weeks  Acute effect of anti-depressant drugs can be worse depression when first start taking the drug • Perhaps it’s not the acute effect of elevating monoamines, but a chronic downstream effect caused by this

Answer 145

• Could be change to sensitivity to monoamines in the brain • In particular, for serotonin receptors, too many 5HT1A on pre-synaptic neurons and 5HT2A receptors on post-synaptic neurons which have regulatory effects in the pre-synaptic neuron • Chronic elevation of 5HT causes these receptors to be reduced over time and their sensitivity reduced • In metabotropic receptors, heightened stimulation of 5HT2A receptors (and other receptors too) causes the neurons to initiate other cellular changes e.g. gene expression o Upregulation of other receptors o They start making hormones (called trophins) that initiate formation of new synapses, or that cause the growth of new neurons • Link to depression may not be amount of serotonin made, but number of receptors on the neurons • This normalises synaptic function

Answer 146

Cocaine, amphetamine

Answer 147

Beta-blockers

Answer 148

MDMA/ecstasy, LSD

Answer 149

Ketamine, PCP

Answer 150

Benzodiazepenes, alcohol

Answer 151

Heroin, morphine

Answer 152

THC in cannabis

Answer 153

• L-Dopa and subsequent production o Tyrosine is turned into L-Dopa through tyrosine hydroxylase action o L-Dopa is turned into Dopamine through DOPA carboxylase action o Dopamine is turned into noradrenaline through Dopamine beta-hydroxylase action

Answer 154

* Parkison’s disease is characterised by a loss of dopamine producing cells in the substantia nigra * Chronic disease that occurs during a lifespan that has no cure and dopamine producing neurons in substantia nigra die slowly until the person dies

Answer 155

• L-Dopa is a precursor for dopamine, and when given to Parkinson’s patients will increase dopamine production o Improves characteristic shuffling gait but amplifies walking movements and exaggerates head movements

Answer 156

• Stress is a process of how you respond to changes that push homeostasis out of wack

Answer 157

Intrinsic or extrinsic adverse forces

Answer 158

* Early work on the physiology of the response to stressors in the 1930s * Later popularised the concept of stress

Answer 159

o Eustress  Stress that enhances function (good motivating stress)  Mild, brief, controllable experience with stressor  Perceived as pleasant, enables growth  Controllable stress

Answer 160

o Distress  Persistent stress that is not resolved through coping or adaptation  Severe, protracted, uncontrollable experience with stress  Leads to chronic diseases

Answer 161

o Determined by the disparity between expectations and experience, and the resources to cope

Answer 162

o Psychological stressors |  Expectations put on individuals by others or themselves

Answer 163

o Physical stressors |  Environmental stressors

Answer 164

• Biological need for homeostasis o Maintenance of an internal state within certain parameters whilst dealing with external changes • Environmental factors continually disrupt homeostasis o Body has to use energy to maintain homeostasis

Answer 165

• Negative feedback maintenance of homeostasis  There is a set point that the system tries to maintain  There are receptors in the body that can detect the changes taking place  There is a control centre which is analysing the body state and deciding what action needs to be taken  There is a way of switching off the compensatory responses when the correct level of the variable has been reached

Answer 166

o Positive feedback (amplification cycle) |  A behaviour causes another consequence and this consequence encourages the behaviour

Answer 167

o Negative feedback (dampening cycle) |  A behaviour causes a consequence and that consequence reduces the behaviour

Answer 168

1. Alarm 2. Resistance 3. Exhaustion

Answer 169

1. Alarm o Initial response o Fight or flight- Immediate short-term responses to crises o Main output: adrenaline from adrenal medulla  First hormone released  Accelerated heart rate and respiratory rate  Changes in circulation -from skin to muscles  Increased energy use by all cells  Mobilisation of glucose reserves  Perspiration to cool the body o Rapid response o Under control of the sympathetic nervous system o Increased secretion of adrenaline and noradrenaline from the adrenal medulla

Answer 170

o Long-term metabolic adjustments  Glucocorticoids are major hormones of the stress response • Glucocorticoids diffuse among tissues and: o Increase release of energy stores from reserves, which could be fats or glycogen o Released as part of HPA • Result in: o Mobilisation of the remaining energy reserves: lipids are released by adipose tissue: amino acids are released by skeletal muscle o Conservation of glucose: peripheral tissue (except neural) breaks down lipids to obtain energy o Elevation of blood glucose concentration- liver synthesises glucose primarily from other carbohydrates and amino acids  Other hormones include growth hormone, adrenocorticotropic hormone and mineralocorticoids (which conserves salts and water) o Slow phase

Answer 171

o Collapse of vital systems o Maintaining the stress response is expensive and the body’s resources have been depleted o If the stressor has been dealt with, then the body can begin a period of recovery o If the stressor has not been dealt with, the body enters the exhaustion phase, and the body cannot maintain normal function  Diseases start to appear • Cardiovascular disorders…

Answer 172

• Somatic nervous system o Brain/spinal cord o Voluntary movements o Most neurons are Acetylcholine neurons and they release them on the skeletal muscles which bind to nicotinic receptors

Answer 173

• Parasympathetic nervous system o Sacral cord o Calms the body down o Acetylcholine system which binds onto another acetylcholine nerve which releases acetylcholine that acts on smooth muscle

Answer 174

``` • Sympathetic nervous system o Thoracolumbar cord o System located in the brain stem o Almost instantaneous o Alarms the body o Main neurotransmitters of sympathetic nervous system-  Acetylcholine • Nicotinic receptors o Muscles (neuromuscular junction) o Other neurons • Muscarinic receptors o Target tissues • Acetylcholine comes out and triggers other symptoms (such as release of adrenaline by activating the adrenal medulla, trigger noradrenaline neuron in external ganglia which release noradrenaline in major systems of the body )  Noradrenaline • Alpha 1 and alpha 2 adrenoreceptors o Alpha 2 autoreceptors inhibit the release of noradrenaline from presynaptic neurons when noradrenaline binds to it (negative feedback system) • Beta adrenoreceptors • Dopamine receptors  Adrenaline • Alpha 1 and alpha 2 adrenoreceptors • Beta adrenoreceptors • Dopamine receptors ```

Answer 175

* Noradrenaline also released in brain * Major nucleus in brain is the locus coeruleus- main source of noradrenaline * Locus coeruleus activity is associated with arousal, vigilance, reaction speed * Locus coeruleus activity increases during fright and fear, and in pain * Central noradrenaline activity is important for arousal, memory, attention and sensory processing as release noradrenaline in the amygdala, hippocampus and other forebrain areas

Answer 176

``` Increased arousal, alertness Increased cognition, vigilance and focused attention Suppression of feeding behaviour Suppression of reproductive behaviour Containment of the stress response ```

Answer 177

Oxygen and nutrients directed to CNS Altered cardiovascular tone, increased blood pressure and heart rate Increased respiratory rate Increased gluconeogenesis and lipolysis Detoxification from toxic products Inhibition of growth and reproductive systems Containment of the inflammatory/immune response

Answer 178

• Hypothalamic-pituitary-adrenal axis o Triggered at level of hypothalamus where hormone called corticotropin releasing factor (CRF) is released from hypothalamus which diffuses through the blood into the pituitary o In the anterior pituitary, CRF triggers release of adrenocorticotropic hormone (ACTH) which diffuses down the blood into the adrenal glands, which triggers the release of the glucocorticoids o Glucocorticoids are dumped into the bloodstream and go throughout the body

Answer 179

Corticosteroids

Answer 180

Generates emotional changes

Answer 181

Triggers sympathetic response

Answer 182

Increases arousal, hypervigilance

Answer 183

• Positive feedback regulation of CRF o Sympathetic nervous response is triggered which releases noradrenalin o Noradrenalin triggers CRF release, which in turn triggers release of more noradrenalin o Activation of sympathetic system seems to trigger activation of CRF and vice-versa o Quick mobilisation

Answer 184

• Negative feedback of the HPA axis o The hypothalamus, hippocampus and cortex all contain glucocorticoid receptors -glucocorticoid release inhibits further glucocorticoid release o When glucocorticoid levels reach a certain point, the secretion is switched off by cortisol acting on the pituitary and hypothalamus to suppress ACTH release o Stimulation of these inhibits  The release of CRF from the paraventricular nucleus of hypothalamus  The release of adrenocorticotropic hormone  Glucocorticoid from the adrenal cortex

Answer 185

* Stressors mobilise the body and the brain to cope and deal with situations that threaten the integrity of the body * The main function of these responses is to direct resources away from maintenance, regeneration and reproduction, and toward systems that are required for active movement * Stress responses, if continued for a long time, prevent immune action, digestion and reproductive processes

Answer 186

• Sympathetic nervous system drives the fight or flight response while parasympathetic nervous system drives the relaxation system

Answer 187

• First few trials o When stressor kicks in, immediate peak of terror/arousal/emotion o When stimulus persists, adapt to it o When stimulus terminates, affective state changes to opposite of what it was o Then goes back to individual’s baseline • After many trials- o Before stressor, anticipation o When stressor persists, enjoyment occurs- initial peak is reduced o When stressor ends, experience joy- opposite reaction peak is much greater

Answer 188

• Opponent processes model o There are two dynamic responses that work together hold individual into a state o Balance deviations from the state of control by turning on one process and suppressing the other process o Adaptation phase- other process tries to suppress the overactivity of the process that caused the initial peak o When first process turned off as stimulus is over, only second counteracting process is left- therefore results in exaggeration of counteracting process o When have done a lot of trials, anticipation makes counteracting process much stronger and so it kicks in earlier (bigger overexaggerating afterwards)

Answer 189

Lemos et al. • Mice: one group was exposed to uncontrollable stressors and the other to a controllable stressor • Put into chambers (place-preference chambers) o Two chambers, one with a vehicle and the other with a drug o If mouse likes the drug, when given choice to explore the two chambers, tend to spend majority of time in side that gave them the most pleasant experience • Injected a group of mice with CRF • Under controllable stressor mice, mice show preference to box paired with CRF • Under uncontrollable stressor mice, mice avoid box paired with CRF

Answer 190

• Alpha blockers- o Depends on selectivity for receptors o Alpha1 blockers tend to be relaxants or sedative o Alpha2 blockers tend to be anti-depressant or stimulatory o Alpha2 agonists tend to be sedative, used for anxiety and insomnia

Answer 191

• Beta blockers- | o Many cardiac effects, but also reduce anxiety and tremors

Answer 192

o Stimulants and anti-depressants affect NA reuptake or metabolic degradation

Answer 193

• Depression is associated with chronically elevated glucocorticoids o Caused by a loss of negative feedback inhibition of the brain over the HPA axis and higher HPA axis basal activity o Glucocorticoids can have potentially long-lasting effects on the function of brain regions that regulate their release o High levels of cortisol caused by the stress of depression may eventually lead to down-regulation of glucocorticoid receptors in the brain, or to them becoming less sensitive to the feedback signal o Are important for axon and dendrite remodelling o Dexamethasone suppression test  DMX is a glucocorticoid receptor agonist  It normally suppresses cortisol in people without depression and suppresses ACTH release from the pituitary gland  DMX has little effect in depressed people

Answer 194

• Size of hippocampus is smaller- adaptation that is making it harder for brain to regulate stress response o Hippocampus- part of the brain that generates new neurons (neurogenesis) o Stem cells that produce neurons in hippocampus die off under high glucocorticoid conditions o Stop hippocampus from replenishing itself (one of the reasons why it shrinks)

Answer 195

``` o Neurogenesis is promoted by:  Environmental enrichment  Exercise  Brain injury  Abstinence from alcohol  Antidepressant drugs ```

Answer 196

``` o Neurogenesis is inhibited by  Stress/glucocorticoid  X rays  Alcohol  Nicotine  Cocaine and other stimulants ```

Answer 197

• Neurogenesis cycle in unrelieved stress- o Unrelieved stress promotes an excessive release of cortisol that damages neurons in the hippocampus o The damaged neurons are unable to detect cortisol and therefore cannot signal the adrenal gland to stop producing it o The result is a feedback loop in which the enhanced secretion of cortisol further damages hippocampal neurons

Answer 198

• Chronic stress/depression affects other regions important for emotional regulation o Volumetric analysis indicates degeneration in:  Anterior cingulate cortex (ACC), posterior orbital cortex, ventrolateral prefrontal cortices (VLPFC) o Post-mortem analysis reveals  Mainly loss of non-neuronal glial cells in these regions  Loss of dendritic branching and synapses between neurons • In depression, regions like amygdala, orbital cortex and medial prefrontal cortex have increased activity

Answer 199

o When see something fearful, generations activity of sympathetic nervous system, then become emotionally conscious of that response o The autonomic changes, and the resulting action, come before the emotion is experienced o Each emotion produces a different set of physiological responses- this is why two different emotions feel different o This is wrong-Cannon disproved it by removing entire somatic nervous system in a cat and showed that had little impact on emotional responses of the animals  Cannon said that when we perceived fearful stimulus, thalamus relayed activation of sympathetic nervous system (to hypothalamus) and experience of emotion (to cerebral cortex) into 2 different paths • Refuted by Bard, who said that cerebral cortex inhibits emotion whilst hypothalamus is essential for emotion

Answer 200

o Experiment:  Brought people in lab and said they were going to do an eye test  Before eye test needed to take a tablet that would be useful  Some were placebo tablets; others were adrenalin tablet (would generate arousal response)  Some with adrenaline told that there would be side effects with the pill and listed the side effects of it, the others weren’t told  In waiting room, an experimenter acted as if he was really happy  In other waiting room, an experimenter acted as if he was really angry (fear provoking environment)  After they took the eye test, were told to take an emotional survey  People who were given placebo tablet didn’t really show difference in emotional state  People who were given adrenaline but were told about side effects did not express difference in their emotional state  People who were given adrenaline but not told about side effects were surprised and showed strong change in emotions • People who were in room with happy person reported that they were happy • People who were in room with angry person reported that they were frightened

Answer 201

o Perceive something fearful, which activates the sympathetic nervous system, heightens awareness of physiological arousal, then there is cognitive appraisal of the situation to determine the most appropriate emotion o Emotion is derived from how you appraise the source of the arousal that you’re experiencing o There is one state of physiological arousal which underpins all emotion in the Schachter-Singer theory of emotion, although this is probably not the case as outlined in recent research • Role of appraisal and evaluation o Coping with stress is changed by the way in which one appraises the stressor o Cognitive appraisal  Primary appraisal is evaluating the severity of the stressor  Secondary appraisal is evaluating the ability to deal with it o Appraisal/evaluation can be important factor in feedback control of stress

Answer 202

• Therapeutic use of cognitions o In training how to cope with stressors  Hyperventilation to induce sympathetic response in clinic, then training people how to cope with stress response o Training coping techniques  Problem-focused coping • Manage the stressor  Emotion focused coping • Manage the response to the stressor  Coan et al • Someone put their head into scanner and put tonic burn on their skin • Had 3 groups o Person in scanner going through pain sensation going by themselves, or holding the hand of someone they loved, or the hand of a total stranger o Unpleasant experience if holding stranger’s hand or by themselves o Less unpleasant when holding hand of person they love

Answer 203

Stress vs anxiety- • Stress- the condition which you are experiencing • Anxiety- the emotion about the stress/anticipation

Answer 204

General anxiety disorder- • Months of excessive anxiety and worry • Worry is out of proportion to the event, pervasive and excessive, difficult to control • Accompanied by muscle tension, hyperarousal and symptoms of the fight or flight response

Answer 205

Panic disorder and agoraphobia- • Sudden attacks of fear or anxiety in situations of little danger • Symptoms of the flight or fight response, complicated by hyperventilation and worsened by fear of collapse or death • Avoidance, for fear of panic, of situations from which escape is not possible or help is not available

Answer 206

Social phobia- • Excessive and unreasonable fears of being the centre of attention in case of negative evaluation because of looking anxious or doing something embarrassing • Situations that could lead to scrutiny or evaluation (social functions…) are avoided or endured with intense anxiety

Answer 207

OCD- • Obsessions are thought, images or impulses that occur repeatedly, are instrusive and distressing and can’t be supressed or neutralised • Compulsions are repetitive behaviours used to control or neutralise the obsessions and prevent the harm and reduce the anxiety, but which are excessive and disabling

Answer 208

``` Post-traumatic stress disorder • Exposure to trauma • Recurring images of the trauma • Distress triggered by similar events • Persistent hyperarousal, avoidance of cues ```

Answer 209

Can fear learning be eliminated? • Experiment by Nader, Schafe and Le Doux 2000 o Rats conditioned to fear a tone CS (paired tone with a footshock) o Retrieval test  Half rats given CS during this test, others no CS  Of these, some given placebo (ACSF), some given high dose anisomycin (protein synthesis blocker) into amygdala, some given low dose o A day later, made one group reexperience CS-US pairing (retrieval group)  Gave some placebo, gave other anisomycin o The other group (the control group) did not reexperience the CS-US pairing a day later  Gave some placebo, gave other anisomycin o All groups tested for fear to the CS two days later after the initial pairing o Anisomycin reduces CS fear if it is given after CS retrieval o Anysomycin has no effect on CS fear if the CS is not presented in the retrieval trial • Suggests that memories pass through a sensitive phase when they are retrieved and that they need to be reconsolidated every time • Possible to target these memories while they’re labile and destroy them • Occurs in implicit learning and explicit learning

Answer 210

``` Fear: =Brief =Present/imminent =Specific/clear threat =Facilitates escape ``` ``` Anxiety: =Prolonged =Future focused =Diffuse or poorly defined threat =Promotes avoidance, caution and hypervigilance ```

Answer 211

• A series of structures linking the hypothalamus and the cortex important for emotion and memory o A loop • Core structures are: o Cingulate gyrus  Modifies behaviour and emotions o Hippocampus  Involved with learning and memory, the recognition of novelty and the recollection of spatial relationships ----- Outputs go through fornix, then mamillary bodies, to septal nuclei, to hypothalamus, to ventral striatum and to frontal lobe o Parahippocampal cortices  Helps modify the expression of emotions o Amygdala  Influences behaviour and activities so that they are appropriate for meeting the body’s internal needs o Fornix  Transmits information from the hippocampus and other limbic areas to the mamillary body o Septal nuclei o Mammillary bodies  Transmits information to and from the fornix and thalamus o Anterior thalamus o Orbitofrontal (ventral prefrontal) o Medial prefrontal cortices -------Nucleus accumbens

Answer 212

• Amygdala + hippocampus project into the thalamus which projects to hypothalamus which projects to the singular cortex (limbic cortex) which projects back down along inside line of temporal lobe and then back down to amygdala + hippocampus- known as Papez circuit (no functional significance)

Answer 213

* Organises the emotional experiences between what we’re thinking and what we’re feeling * Important for learning about emotional responses and their appropriateness

Answer 214

o Amygdala to hypothalamus: sympathetic o Amygdala to vagal nucleus: urination and defecation o Amygdala to parabrachial nucleus: breathing o Pontine reticular: startle o Periaqueductal grey: freezing and analgesia o Facial motor nucleus: expressions of fear

Answer 215

• Amygdala important for rapid detection of threats and the emotion surrounding these threats

Answer 216

• Context: o White rats are placed into a chamber and allowed to explore for 2 minutes o A tone or noise is presented for 30 seconds o When the tone terminates, the rat receives footshock o Rats taken back out of chamber after a few trials then placed back in to test for fear of the context o Rats are tested for fear of the tone in a novel context o The defensive response time of freezing is used to measure fear o Show that rats show fear through conditioning through context • Brain lesions: o Canular in brain of rat under anaesthesia and release a chemical which will make experimentally induced lesion o Examined which parts of the brain were important for parts of the fear learning system o Non-lesioned rats showed normal fear and extinction o Cortex lesioned rats showed normal fear and extinction o Amygdala lesioned rats showed no fear at all o Hippocampus lesion rats showed fear of cue preceding fear only but failed to learn about place where fear occurred o Can independently learn about cue which proceed fear and place where fear took place

Answer 217

• People with brain damage were given conditioning trials in which colours and weak tones (CS) were paired with loud noise (US). • Conditioned fear was measured by an automatic response: the galvanic skin response • At end of training the subjects were asked these questions: o How many different colours did you see? o Tell me the name of the colours? o Which colours were followed by the loud noise? • Patient A- those who had amygdala damage o The patient with amygdala damage was not able to acquire the conditioned fear response but could recall the events of training • Patient H- those who had hippocampal damage o The patient with damage to the hippocampus acquired the conditioned response but could not recall the training items • Patient AH- those who had both amygdala and hippocampal damage o The patient with both A and H damage could not feel fear or recall

Answer 218

• Formation: o Emotional event goes to sensory systems, which then relay that event to the explicit memory system (medial temporal lobe) which forms a memory about emotion, and the implicit memory system (amygdala) which forms emotional memory  Connections to brainstem neurons containing noradrenaline, dopamine, serotonin and acetylcholine lead these neurons to release their chemicals in widespread areas, helping facilitate the formation of memories about emotions

Answer 219

• Retrieval: o Emotional event goes to sensory systems, which then relay that event to the explicit memory system (medial temporal lobe) which retrieves a conscious memory of the emotional event, and the implicit memory system (amygdala) which expresses emotional response

Answer 220

``` • Nuclei in amygdala: o Basolateral nucleus  Lateral nucleus  Basal nucleus  Accessory-basal nuclei o Corticomedial amygdala o Central nuclei ```

Answer 221

o Pavlovian fear conditioning is based upon neuroplasticity within the lateral nucleus of the amygdala o Infusion of drugs that block neuroplasticity into the amygdala block fear conditioning

Answer 222

o Process:  Information about the unconditional stimulus enters the lateral nucleus and this can automatically excite the outputs of the central nucleus  If this fires at the same time the neurons are firing that encode the conditioned stimulus (context), they bind together through process of long-term potentiation  After repeated pairings, the conditioned stimulus can excite the same neurons in the lateral nucleus as the unconditioned stimulus

Answer 223

• For simple stimuli, fear conditioning can be a rapid process that does not require conscious appraisal (low road) o Emotional stimulus goes straight from sensory thalamus to lateral nucleus of the amygdala o Provides a rapid but fuzzy sensory representation to the amygdala

Answer 224

• Learning about more complex stimuli (e.g. contexts) requires longer processing time and post-conditioning consolidation periods (high road) o Emotional stimulus goes from sensory thalamus to sensory cortex and then to the lateral nucleus of the amygdala o Provides a slow but detailed sensory representation to the amygdala

Answer 225

• Extinction is due to the Associative-Loss hypothesis o Assumes that presenting the CS alone results in erasing the underlying association o NOT TRUE

Answer 226

• Extinction is due to new learning o New learning- learn that nothing is happening after cue- inhibits original learning o Behaviour is results of the competition between the relative strength of the CS-No US learning from extinction and the CS-US learning from conditioning o Evidence from extinction of conditioned fear  Repeated presentations of a CS without the US result in loss of the CR during the extinction session  There is also a maintained reduction in CR when tested again the next day  Therefore there is a within session extinction effect, and a between session extinction effect  Extinguished fear can return under many conditions such as change in test context (renewal), re-experiencing the US (reinstatement) or the passage of time (spontaneous recovery)

Answer 227

 Medial prefrontal cortex is important for deciding whether individual should be frightened/anxious or not: good for controlling emotions  Medial prefrontal cortex does not have a role in extinction learning but through consolidation of extinction memory, especially through the Infralimbic prefrontal cortex mediated through NMDA receptor-dependent plasticity and epigenetic processes  Not important for within session extinction effect (learning during a session to be unafraid) but important for the between session extinction effect (when two extinction sessions are done and the memory from the first one carries over to the second one)  Does not play a role in acquisition  Medial prefrontal cortex has synaptic connections to basolateral nuclei, and receives info from and to BLA during extinction, but only from during acquisition

Answer 228

• Acquisition o During acquisition a CS paired with shock has its synaptic connections to cells in lateral nucleus strengthen (glutamatergic neurons) o This allows the CS to put excitatory drive on to central nucleus

Answer 229

o During extinction, a previously conditioned CS is presented without the US o As a consequence, its synaptic connections with cells in the basal nuclei are strengthened (neuroplasticity is important in this regard)  Basal nucleus important for extinction learning is because it has inhibitory intercalator cells which are GABAergic inhibitory cells and they suppress/inhibit central nucleus  Medial prefrontal cortex gates the inhibitory system • Synaptic changes connecting the CS to the basal nucleus support within-session extinction but between-session extinction requires the medial prefrontal cortex • Rats with damage to the prefrontal cortex can display within-session extinction but cannot display between session extinction: thus medial prefrontal cortex plays a major role in the long term memory for extinction • Suppresses emotions and controls them o Output of basal nuclei cells drive intercalator cells (IC) o These cells then inhibit central nucleus expression o Neurons within the central nucleus, which are all GABAergic, are extensively interconnected providing strong local inhibition o This results in the CS inhibiting the output of central nucleus

Answer 230

• Simple phobias o Some stimuli/thoughts more likely to become phobic than others o Higher baseline rate of arousal to these stimuli o Only need a small US to trigger as biologically ready to be excessively fearful of stimulus • PTSD o Very large USs/trauma • Panic attacks o Physiological signs of hyperarousal- CS (internal cue) o Fear of panic

Answer 231

Exposure therapy -Expose to stimulus in safe environment Systematic desensitisation (counter conditioning)- - Relaxation is reciprocally inhibitory of fear - Goal is to counter condition a relaxation response to the fear generating CS 1. Train a relaxation response 2. Construct a fear hierarchy - --Rate the aspects/stimuli of the fear that are least-to-most fear generating 3. Counter condition - -Starting with the least fear-provoking stimulus-pair this with the relaxation response. Work up the hierarchy 4. Real world test - -Repeat if fear persists

Answer 232

Benzodiazepenes -GABA A agonists are highly sedative Serotonin-specific reuptake inhibitors - First used as anti-depressive drugs - Prescribed for obsessive-compulsive disorder and some other anxiety disorders, bulimia, anorexia Beta-blockers -Antagonists of beta adrenergic receptors, block hyperarousal symptoms and help people control and manage anxiety

Answer 233

D-cycloserine is a drug that was originally used for tuberculosis treatment that was found to be an NMDA receptor agonist which is important for neuroplasticity - It has no anxiolytic effects by itself - However, it enhances exposure-based therapies due to its involvement in enhancing neuroplasticity and makes the treatment after-effects last longer- less relapse

Answer 234

90% of the brain - Astrocyte - Microglia - Oligodendrocytes

Answer 235

 Major glial cell of brain- form most of structure of brain  Star shaped  Function: • Glue that holds the brain together-provide structural support • They control ionic composition of the extracellular fluid by removing excess potassium ions o Highly dynamic subcellular elements capable of mobility, retraction and extension which can have strong impact on neuronal network by influencing the extracellular diffusion of neurotransmitters • Help break down neurotransmitters in the synaptic cleft which prevents toxic build-up off certain neurotransmitters such as glutamate • Release growth factors which are chemicals involved in the growth and repair of nerve cells • Involved in transporting nutrients into neurons and removing waste products • Astrocytes can increase the brain’s activity by dilating blood vessels thus enabling greater amounts of oxygen and glucose to reach the neurons through production of vasoactive substance • For nutrients o Astrocytes take in glucose and convert to lactate o Lactate as primary energy source for neurons • Form scar material • Forms blood-brain barrier

Answer 236

 Characterised by the expression of glial-fibrillary acidic protein (GFAP)

Answer 237

 Consists of small glial cells which migrate through nerve tissue and remove waste products by phagocytosis • Glial cells are extremely active in the brain-probe brain through extending fibres  Resident macrophages of central nervous system

Answer 238

 Characterised by expression of OX-42 (complement 3b receptor) or Iba-1  Also express peripheral benzodiazepine receptors • Now known as translocator protein, TSPO  Characterised by expression of OX-42 (complement 3b receptor) or Iba-1  Also express peripheral benzodiazepine receptors • Now known as translocator protein, TSPO

Answer 239

 Neuroglial cell of the central nervous system in vertebrates whose function is to myelinate CNS axons  Allow more axons/neurons to be packed into a tighter area

Answer 240

 Myelin basic protein (MBP) or Rip antigen

Answer 241

o Astrocytes and oligodendrocytes come from neural stem cells-  These neural stem cells can branch out into neural progenitors which become neurons • Before birth • But adult neurogenesis can occur in the dentate gyrus in the hippocampus (important for memory and emotional regulation) and subventricular zones  These neural stem cells can branch out into glial progenitors, which can branch out to astrocytes or O-2A cells (these cells can become oligodendrocytes or astrocytes)

Answer 242

o Microglia come from hemopoietic stem cells  These stem cells can branch out into myeloid precursors, which can branch out into monocytes and eventually microglial cells or macrophages

Answer 243

- Support and structure - Synaptic modelling and development - Tripartite synapse - ---Regulate neurotransmitter release - ---Spread excitation - Immune functions

Answer 244

 Astrocytes take in glucose and convert to lactate |  Lactate as primary energy source for neurons

Answer 245

 Neurons cultured without glia produce less synapses  Neurons don’t synapse with each other by themselves on a dish-need glial cells for them to make functional synapses  Glial cells release growth factors that encourage this  Microglia important for proper brain formation  Glial cells can give rise to neurons or guide neurons to their correct location  Astrocytes induce synapse formation as well as oligodendrocytes

Answer 246

• The normal view of synaptic activity is that neurons communicate with each other by releasing neurotransmitters (e.g. glutamate) into a synapse, and these bind to receptors on other neurons • If enough neurotransmitter binds to these receptors, the second neuron is triggered • Glia assist neural activity by physically insulating synapses, by removing excess neurotransmitter from the synapse (to maintain speed of response), and by helping to maintain ionic balance (help maintain neurochemical gradient along postsynaptic neuron) o Efficiency of removal of excess neurotransmitter dependent on astrocyte ensheathing changes • Glia express neurotransmitter transport proteins • Neurotransmitters might be recycled back to the neuron e.g. glutamate is converted to glutamine which is taken up by neurons to be turned back into glutamate

Answer 247

• Neurons communicate via: o Action potentials spreading excitation along a neuron o Then releasing neurotransmitters to stimulate other neurons

Answer 248

o Gap junctions between astrocytes allow the messenger molecule IP3 to diffuse from one astrocyte to another o IP3 activates calcium channels on cellular organelles, releasing calcium action potentials within their glial cell cytoplasm (chemical potential with calcium) o This calcium may restimulate the production of more IP3 and cause release of ATP through membrane channels to stimulate other glia  Adding ATP to culture glial cells induces a calcium response  Microglia are attracted by ATP  Glial cells base their cellular excitability on variations of the calcium concentration in the cytosol

Answer 249

 Tripartite (3 part) synapse • 1. Presynaptic neuron • 2. Postsynaptic neuron • 3. Astrocytes enveloping the synapse • Glia express receptors for neurotransmitters • When these are stimulated by a ligand, cause release of calcium within the cells which causes release of ATP and ligand • Glia also release neurotransmitters that can affect neuronal function o But happens at the scale of minutes and hours

Answer 250

``` o Insulate o Regulate o Resuppply o Respond o React ```

Answer 251

o Immune functions  Brain is an immune privileged area of the body  Microglia are resident immune cells • Surveillance, response, phagocytosis • Release immune signalling molecules (cytokines) in response to stress signals • Attract other immune cells into the nervous system • Affect function of astrocytes and neurons  Glia help recovery in brain disease • Remove dying or diseased neurons through phagocytosis or triggering cell death (apoptosis) o Primary response of brain to damage is microglia response o Triggered via cytokines or other molecules • Guide new axonal growth into damaged area o Release of neurotrophic hormones

Answer 252

o But sometimes can also trigger maladaptively and attack healthy neurons and kill them  Glia are involved in most neuropathologies and can be harmful • Most neurodegenerative disorders are associated with abnormal glial activity o Brains of Alzheimer’s and Parkinson’s patients show increased glial activation o Increased cytokine activity in neuropathologies • Many factors released by microglia can be neurotoxic o Many cytokines can trigger cell death

Answer 253

• Treatments that reduce glial activity reduce: o Onset of neurodegenerative diseases, negative symptoms of schizophrenia, addiction…  Dependence forming seems dependent on glial activation

Answer 254

• Immunohistochemistry relies on the fact that the immune system produces antibodies specific to type of antigen

Answer 255

o Have 2 variable domains (which recognise specific types of shape of molecule) and a constant domain o Will bind to antigen via the 2 variable domains  Variable regions differ in amino acid sequences at the antigen-binding site and are responsible for the diversity of Ab specificity o Constant domain is the same for all antibodies made by that species

Answer 256

• Isolating antibodies specific to the component want to analyse o Isolate molecules on surface of cell, put them in solution, concentrate them and inject in animal o Animal will generate antibody in response to that foreign substance o Isolate the antibodies produced which will be specific for the thing you want to study

Answer 257

o Immunofluorescence  Add primary antibody specific (from another animal) to thing you want to study  Add secondary antibody (from another another animal) conjugated to fluorophore which is specific to primary antibody’s constant domain so that it can bind to it  Visualise using fluorescence microscopy

Answer 258

o Immunohistochemistry  Add primary antibody  Add secondary antibody conjugated to HRP  Add chromogen, HRP catalyses reaction to produce coloured precipitate  Colour precipitate accumulates around location of antigen. Visualise using Brightfield microscopy

Answer 259

o Double labelling (2 antibodies at the same time for mosaic images)  Can use primary antibodies raised in different animals specific to different antigens  Secondary antibodies are specific to the antibodies of species of the primary antibodies  Secondary antibodies have different coloured fluorophores, stimulated by different wavelengths of light  Can see anatomical distribution of stuff in the brain and how they change

Answer 260

• Isolated out human astrocytes from post-mortem people • Injected them into the brains of mice • Wanted to see what human astrocyte cells would do to mouse behaviour • Human astrocytes normally grown in rat mouse o Made a half-mouse half-human in the brain • Gave behavioural tests to see what changes occurred • Animals became smarter and learned things more rapidly with human astrocytes o More rapidly acquired fear conditioning o More likely to remember platform in Morris Water Maze task • Shows importance of astrocytes to development of brain

Answer 261

• Resting potential of the charge across the membrane is about -70 mV (slightly electrically negative)

Answer 262

• If membrane threshold is at -55mV, then the postsynaptic neuron fires and an action potential occurs

Answer 263

o Inhibitory neurotransmitters make the voltage potential more negative

Answer 264

o Excitatory neurotransmitters make the voltage potential less negative and closer to the threshold for stimulating an action potential

Answer 265

 Temporal summation • There’s a sufficiently fast barrage of inputs from a single neuron • Timing of the impulses hitting patch of membrane occurs really quickly which makes it more likely that the postsynaptic neuron will fire  Spatial summation • There’s synchronised inputs from multiple synapses in a small region • Several neurons which converge on local part of postsynaptic neuron membrane all presenting inputs in the same space

Answer 266

• Rate law- the strength of a stimulus is represented by the rate of firing of an axon: the size of each action potential (how much neurotransmitters is put in at once) is always constant. o Because the action potential is an ‘all or nothing’ response, there is no information about the intensity of the stimulus from the action potential size/amplitude o Therefore, information about stimulus intensity comes from the action potential rate or frequency

Answer 267

• Behaviour is controlled by its consequences (law of effect) • Behaviour leading to desirable outcome is strengthened (positive reinforcement) • Behaviour leading to escape from unpleasant consequences is strengthened (negative reinforcement) • We try to maximise pleasant consequences (hedonics/utilitarianism) o Individuals are agents that seek to maximise their pleasure through the selection of their behaviour

Answer 268

• Reinforcers o Energise behaviour to acquire reinforcers o Produce approach (appetitive behaviour-goal directed behaviour) o An animal will learn any arbitrary response to come into contact with reinforcers

Answer 269

1. Dopamine is released by natural rewards 2. Reinforcing effects of natural rewards and drugs of abuse are decreased by dopamine antagonists 3. Reinforcing effects of brain stimulation are modulated by drugs that modulate dopamine 4. Stimulating dopaminergic neurons is reinforcing

Answer 270

• Mesolimbocortical pathway a. Ventral tegmental area to nucleus accumbens, cortex, hippocampus and various regions in the limbic system, olfactory bulbs and neocortex b. Main reward pathway c. Cell bodies originate in the ventral tegmental area and project through the medial forebrain bundle to various structures • Mesostriatal pathway a. Substantia nigra to striatum (caudate and putamen) b. Get dopamine spike before motivated behaviour as well measurable in the mesostriatal system

Answer 271

* When animal experiences natural reward, it will drop a recording electrode which is sensitive for the signal produced by dopamine chemical in the brain * When retrieve reward, get big spike of dopamine in nucleus accumbens

Answer 272

• Early anti-psychotics were specific for the D2 dopamine receptor and block that receptor

Answer 273

o Rats trained to press a lever for food o Some were given extinction (no food after lever press) o Some were maintained on food reinforcement but were given different levels of the antipsychotic pimozide, which predominantly binds to D2 receptors o Found that level of response-reinforced behaviour greatly decreased across trials o Doze mattered- most doze makes least response

Answer 274

Intracranial self-stimulation | • However, with these techniques can’t be sure that effect is on one type of neuron only

Answer 275

Reinforcing brain stimulation • Olds and Milner showed that rats will learn to press a lever if it produced electrical stimulation in certain regions of the brain • ICSS- Intracranial self-stimulation • Put electrodes in brains in rats to stimulate various regions of the brain o Make it contingent on rat pressing a lever • Wanted to see if part of brain was a pleasure centre o Found that high rates of self-stimulation were obtained from the septum, amygdala and anterior hypothalamus o Found that moderate levels of responding were elicited from the hippocampus, cingulate gyrus and nucleus accumbens o Greatest rates of self-stimulation was the lateral hypothalamus • Were able to map out parts of the brain responsible for seeking reinforcements

Answer 276

• Kenny et al. 2003 o Drugs that affect dopamine affect ICSS  Have rats press lever and change voltage in stimulator  Wanted to find voltage threshold which would support behaviour o Cocaine seemed to boost the signal and lower minimum threshold whilst anti-psychotics increase minimum threshold

Answer 277

• Microdialysis o Insert a cannular in part of the brain which has a porous tip (allows chemicals to diffuse across by osmosis and sample chemical environment in that part of the brain) o Would stimulate brain and sample chemicals in there o Found that reinforced behaviour was associated with large spike in dopamine (especially in nucleus accumbens) o Can also inject cannula in discrete parts of the brain using stereotaxic procedures  If injected anti-psychotic drugs or dopamine antagonists in the nucleus accumbens, would lose effect of ICSS o Reward system is release of dopamine into nucleus accumbens

Answer 278

* Vigorous- rats will press more than 1000 times per hour * Produces little satiety- rats do not appear to get tired of self-stimulation * Modulated by motivational state- self-stimulation of certain brain regions is modulated by motivational state * Modulated by drugs-drugs of abuse such as cocaine, heroin, nicotine and amphetamine facilitate self-stimulation. Drugs that block dopamine receptors greatly inhibit self-stimulation, even at low doses

Answer 279

• Anhedonia hypothesis o Perhaps dopamine antagonists reduce reinforced responding because they reduce the pleasure of the reward • Problems with hypothesis o Anti-psychotics don’t reduce the pleasure that is experienced from food  Barbano and Cador • Dopamine doesn’t change consumption of food in hungry and sated rats • Chocolate milk is preferred compared to chow no matter whether given anti-psychotic or not when there’s no work required for it

Answer 280

* Channel receptors ChR2 (stimulated by 470nm) and NpHR (stimulated by 589nm) which are like the channels in retina which are sensitive to light * When stimulated, open up an ion channel and change polarisation of cell they’ve been expressed in * ChR2 (channelrhodopsins) is excitatory (allows sodium to come in), NpHR (Halorhodopsin) is inhibitory (allows chlorine to come in) • Optogenetics steps; 1. Piece together a genetic construct 2. Insert construct into virus  Virus constructed so only affect certain types of specific cells  Virus causes cell to generate its own channel proteins- makes the specific neuron wanted make its own proteins  Virus infects all neurons- but only makes the ones it targets make specific proteins 3. Inject virus into animal brain; opsin is expressed in targeted neurons 4. Insert optrode, fibre-optic cable plus electrode 5. Laser light of specific wavelength opens specific ion channel in neurons * Neuron specific technique and can stimulate certain parts of one neuron as well depending on where you put the light * Much more specific than electrical stimulation

Answer 281

• Rats were stimulated in nucleus accumbens using optogenetic array • Sufficient to reinforce lever pressing behaviour o Optical stimulation of dopaminergic ventral tegmental area neurons expressing ChR2 is sufficient to reinforce behaviour

Answer 282

o Signals when significant things are about to occur  Behaviour is motivated to respond to this predicted outcome • Schulz (1997), Day et al. (2004) o Paired signal with the arrival of food  Classical conditioning a CS to a food US o Measured neural activity of dopamine under 3 conditions  Reward occurs without CS  CS occurs prior to reward  CS occurs and the predicted reward does not arrive o The CS (not the food) causes dopamine release when classical conditioning is done  Normally, without classical conditioning, food makes dopamine pulse  Predictive system

Answer 283

o Allocates response effort and choice behaviours -organises behaviour in order to come into contact with good things  Make rats press lever with progressive ratio system (number of lever presses required to obtain rewards increases after every reward)  Break point is the ratio at which participants stop • With amphetamines, will work much harder for a reward than usual  Also, control rats will work for better food even with undesirable free food (such as chow), but dopamine depleted rats will just take the free food

Answer 284

• Dopamine in the striatum predicts reinforced behaviour (Hollerman et al. 1998) a. Activity of single dopamine neurons in the striatum recorded b. Animals trained in a discrimination task i. If a Go signal- response is rewarded ii. If a NoGo signal- non response is rewarded c. Striatal dopamine neurons predict rewarded movement i. Spike in dopamine activity until reward is initiated ii. Part of voluntary decision-making process of animal is the buildup of dopamine inputs in the striatal system by the mesostriatal system which then drives approach behaviour for reinforced activities 1. Important for learning when rewards will occur 2. Important for motivating behaviour and return to reward seeking behaviours

Answer 285

• Schlaepfer et al. a. Got people who had untreatable depression b. Implanted cannular into nucleus accumbens c. Reported no euphoria from nucleus accumbens stimulation but it changed their motivation i. Wanted to do things that they considered pleasurable d. Dopamine motivates exploration and motivates desire to contact rewarding experiences

Answer 286

* Is not important for the pleasure from the rewards * Signals the significance and salience of rewards * Motivates/energises effort to obtain rewards

Answer 287

1. Rewarding effects of drug 2. Social learning 3. Individual expectations of use 4. Cultural influences 5. Social feedback/peer group selection 6. Individual life goals

Answer 288

1. Total abstinence 2. Rare/social use 3. Heavy social use/early problems 4. Heavy problem use/early addiction 5. Clear addiction/dependency

Answer 289

• Positive reinforcement o All drugs of abuse produce reinforcement, at least initially o All drugs of abuse activate mesolimbic dopamine (although these effects may be indirect and different drugs have different primary targets) • Negative reinforcement o Loss/removal of unpleasant or aversive state

Answer 290

1. Escalating use a. Tolerance to the drug 2. Withdrawal a. Hyperactivation of arousal and stress b. Anhedonia 3. Craving or compulsion a. Cue elicited activation of limbic and reward symptoms 4. Loss of control a. Less activity of frontal regulatory systems

Answer 291

- Tolerance - --Reduction of the positive effects of drugs - ----Behavioural - ----Pharmalogical - Withdrawal symptoms - --Increase in the negative effects of the drug

Answer 292

o Acute pharmacological tolerance (while taking the drug)  Negative feedback system at the level of the synapse-recycling system • Neurotransmitters are released and bind onto receptors • Have effect on postsynaptic membrane but then active membrane receptors become silenced after bound to neurotransmitters -they are made inactive • The now inactive receptors get taken off the cell membrane and endocytosed, so they are recycled and put back on the cell surface  Loss of active receptors (temporarily)

Answer 293

o Chronic pharmacological tolerance (after chronic use of drug)  Repeated stimulation of receptors causes the neuron to downregulate the production of new receptors  When receptors get endocytosed, they no longer get recycled and reused  Loss of total receptors

Answer 294

o Opiates- Gutierrez-Cebollada et al. 1994  Heroin addicts overdose more in unfamiliar surroundings  Greater effect of heroin if addicts self-inject rather than receive passive infusion

Answer 295

o Alcoholic drinks  Remmington et al. 1997 • People feel less drunk if drinking beer than a novel blue alcoholic drink • Examined the role of cues arising from the drinks themselves • Subjects got either a familiar drink (beer) or an unfamiliar drink with equal alcohol content • If drink cues produce tolerance, measures of intoxication should be reduced following consumption of a familiar drink

Answer 296

o Pavlovian conditioning and tolerance  Pair context in which you take it and result of drug use together after a while  Conditioned tolerance occurs • Cues associated with drug use weaken the physiological responses to the effect of the drug, producing tolerance

Answer 297

• Standard Pattern of Affective Dynamics in drug use o Drug is stimulus event o Hedonic state from taking the drug forms the initial peak, followed by an adaptation phase o When drug finishes, get a crash afterwards (because body was trying to counter drug effects to maintain homeostatic balance) • In opponent process, pharmacological tolerance reduces the high you get from a drug, whilst conditioned (behavioural) tolerance triggers the opponent process and tries to balance this high (because of prediction that homeostatic processes will be challenged by drug) and becomes larger • When drug taken frequently, crash becomes lower and lower because the high isn’t as big anymore and the behavioural system overcompensates and therefore you don’t get much high but get drastic lows

Answer 298

o Temporary increase in activity at dopamine, GABA, serotonin, opioid etc receptors o Temporary increase in systems driving stress responses and recuperative responses

Answer 299

o Long lasting decrease in dopamine, GABA, serotonin, opioid peptides etc. results in loss of pleasure from drugs or other activities o Long-lasting increase in systems driving stress responses and recuperative responses drives withdrawal symptoms

Answer 300

• Chronic drug use causes plastic changes to the brain that can result in o Diminished effect of the drug o Disordered mood • Drug use then acts as a negative reinforcer o People take drugs to instrumentally manage their moods • Problem o Need more drug to manage mood o The drug use causes further plastic changes to the brain

Answer 301

Poor decision-making in addicts • Less behavioural flexibility in addicts • More risk taking in gambling tasks by addicts • Less self-control in addicts

Answer 302

• In normal conditions o Reward system (ventral striatal system) that stimulates drive (orbital frontal cortex) o Memory (limbic system) triggers reward system based on types of experiences that you have o All of this is under control of medial prefrontal cortex that normally regulates this system

Answer 303

• Addiction is a dysregulation of the way in which certain systems of the brain work together which regulate appetitive behaviours

Answer 304

• In addiction o Control mechanism is offline and get hyperactivity of subcortical structures (reward, drive and memory) such that there is strong learning to cues associated with drugs that stimulate reward pathways and stimulate drive to get more drugs o Dysregulated activity

Answer 305

• Wetherill et al. 2014 o Twenty treatment-seeking, cannabis-dependent individuals (12 males) underwent event-related blood oxygen level-dependent functional magnetic resonance imaging during exposure to 33-ms cannabis, neutral, and aversive cues presented in a backward-masking paradigm o When shown the images, all cues activated the insula cortex and amygdala  Insula cortex important for bodily sensations and disgust o Only cannabis cues activate the ventral striatum  People also report craving when they see these cues  Drug cues activate brain reward regions (Nacc) and limbic systems (ACC) and motivational regulation regions of the prefrontal cortices (OFC) • For orbital frontal cortex, the ability of cues to activate the orbital frontal cortex is related to how long they’ve been taking the drug

Answer 306

• Main role of orbital frontal cortex seems to be to provide the drive for taking the drug

Answer 307

• In medial prefrontal cortex, get a shrinkage and loss of it with increased drug use, causing less self-control and less emotional and motivational regulation

Answer 308

• Engagement of evolutionary ancient mechanisms: our animal ancestors get addicted to (seeking of fermented fruits by elephants) • Four major processes with repeated drug exposure: o Neuroadaptation 1- sensitization in the dopamine pathways o Neuroadaptation 2- brain adjusts to the presence of a drug causing emotional turmoil of drug withdrawal o Neuroadaptation 3- Often repeated actions become habits o Neuroadaptation 4- Addicts make poor decisions • Genetic vulnerability- some genomes lead to a more addiction prone brain • Developmental vulnerability- adolescents might be more prone • If there are clear consequences, will change addiction behaviour quickly

Answer 309

• Rat Park study o Put morphine in rat water bottles and make them become dependent on the morphine o Put rats in social housing (naturalistic environment) vs in isolated cages  In social housing environment, rats did not touch morphine water bottles as had other stimulation  In isolated cages, rats became rapidly dependent on morphine

Answer 310

• Choice and addiction-Ahmed o Choice as a sieve for drug addiction experiment  Rats can choose to self-administer cocaine or sugar water  When given a choice over two rewards, rats choose sugar water over cocaine mostly

Answer 311

• Hypofrontality is a state of decreased cerebral blood flow (CBF) in the prefrontal cortex of the brain due to neuronal changes and shrinking of these regions.

Answer 312

o A phenotype is an adaptation when:  It has many design features that are complexly specialised for solving an adaptative problem  These phenotypic properties are unlikely to have risen by chance alone  They are not better explained as the by-product of mechanisms designed to solve some alternative adaptative problem

Answer 313

o Catabolic- releasing and using energy  Breaking down large molecules into smaller ones, releasing energy  Associated with weight loss

Answer 314

o Anabolic- acquiring and storing energy  Creating new molecules from smaller ones, storing energy  Associated with weight gain

Answer 315

``` o What we eat:  Carbohydrates (most eating)  Lipids  Proteins  Alcohol o What we expend  Thermogenesis  Physical activity  Basal metabolic rate (most energy used for this) ```

Answer 316

• Set point theory- o There is a preferred body weight that the brain defends  If underweight • Physiological changes to reduce catabolism • Behavioural changes to increase food consumption  If overweight • Physiological changes to increase catabolism • Behavioural changes to decrease food consumption

Answer 317

o Kennedy’s (1953) adiposity theory |  Long term regulation of body mass by signals released from fat stores

Answer 318

o Gibbs, Young and Smith’s (1973) satiety model |  Meal initiation and termination from signals released from gastrointestinal tract

Answer 319

• The medulla can sense if there’s just been a meal by detecting an increase in blood sugar, hormones from the gut, and whether the stomach is full • Liver- releases hormones (that vagal nerve detects) which is detected by NTS (nucleus of solitary tract in medulla) • Stomach- releases hormones and stretches when full, changes that vagus nerve detects which is then passed on to the by Nucleus Tractus Solitarius (nucleus of solitary tract in medulla) and area postrema. Changes firing rate of ventromedial hypothalamus o Stomach contractions also associated with hunger • Blood sugar detected by nucleus of solitary tract in medulla to see if there’s too much or too little o Liver sends information regarding blood glucose levels to the brain via the hepatic branch of the vagus nerve, which ascends to the nucleus of the solitary tract (in the brainstem) and hypothalamus.

Answer 320

o Released from fat cells  Leptin release is proportional to amount of fat in the body  Indicator of body fat o Negative correlation between plasma leptin and appetite  High leptin= lower appetite, higher metabolism o Long term effects o Leptin is a signal for satiety o Acts on receptors in hypothalamus and inhibits NPY

Answer 321

o Released from pancreas in response to elevated blood sugar  Causes tissue to take up glucose from blood o A good signal for a recent meal of that there is sufficient energy reserves in the body o Rapid signal o Satiety signals- just had food or there’s enough food in body o Released by pancreal gland

Answer 322

o Released from the stomach o Stimulates appetite, inhibits metabolism o Secretion depends on nutritional state o Rapid release with close timing to eating behaviour o Broken down into obestatin which stimulates metabolism (opposite effect)

Answer 323

• The hypothalamus can detect how much body fat there is, and whether a meal has been eaten o Arcuate nucleus of the hypothalamus o Responds to leptin, insulin and Ghrelin

Answer 324

• The lateral hypothalamus stimulates appetite (orexic) o When in rest/digest, the lateral hypothalamus will stimulate parasympathetic nervous system responses organised at medulla level (storing of energy stores)

Answer 325

• The paraventricular nucleus inhibits appetite (anorexic) o When in fight of flight, the paraventricular nucleus will be operating with the pituitary gland to stimulate the sympathetic nervous system responses organised at medulla level (burning of energy store)

Answer 326

* Ghrelin causes the arcuate nucleus to stimulates the later hypothalamus and inhibits the paraventricular nucleus * Leptin and insulin causes the arcuate nucleus of the hypothalamus to inhibit the lateral hypothalamus and stimulate the paraventricular hypothalamus

Answer 327

• Our appetite for food is only vaguely related to our need for energy o Conditioned to be hungry at certain times of the day  Neurons in the basolateral amygdala, medial frontal cortex and lateral hypothalamus were selectively activated by the conditioning procedure

Answer 328

• Mesolimbocortical dopamine and appetite o The arcuate nucleus stimulates the lateral hypothalamus, but the lateral hypothalamus is a strong stimulator of the ventral tegmental area  This system stimulates dopaminergic reward seeking behaviour and promotes learning

Answer 329

o Weingarten 1983  Pavlovian conditioning was used to teach rats an association between an arbitrary external cue and good (every time he gave them food, a tone played) • Times of meals were varied across the day • When tone came on, would run to food  After a couple of days, just put the food in there (free bowl of food) with no tone to see what would happen, and would only play tone once a day afterwards • Presentation of the conditioned cue elicited feeding by sated animals • Same amount of food was eaten in tone vs no tone, but the tone meal constituted approximately 20% of daily intake, and it was compensated for by a reduction of subsequent intake

Answer 330

o Internal cues of hunger and satiety vs external food or meal-relevant cues and how they drive behaviour  Bring people to lab  Get them to work on the task  Let them free graze on biscuits put in front of them and measure how many biscuits they’d eat -with external cues (such as smelling pizza in the next room), they’d eat more biscuits • For most people, how much they ate was determined if there was an external cue o Obese people are less sensitive to internal cues, and are very sensitive to external cues  Put a cannular down nose into stomach with inflatable balloon in stomach  As people were eating during these experiments, would inflate balloon in stomach  People who are overweight are less sensitive to the sensation of a stretched stomach and will continue to eat even with these internal cues than people who weren’t overweight

Answer 331

o External cues should be divided into  Normative cues • Social cues about meal size, important contextual cues (plate size, portions)  Sensory cues • Smells or sight of food, food paired-cues

Answer 332

o All people are sensitive to normative/social cues  Will eat to the size of the plate  Will eat the same as people around them

Answer 333

 People who are overweight are less sensitive to the sensation of a stretched stomach and will continue to eat even with these internal cues than people who weren’t overweight o Obese people are specifically sensitive to sensory cues

Answer 334

o Motivational state modulates pleasure  Wanting a food makes you like it more  Satiety decreases the pleasure of the food o Loss of pleasure of food at the end of the meal is the normal process by which people terminate a meal

Answer 335

• Separate areas encode wanting and liking -KC Berridge Laboratory o Rats had cannulas placed into the Nucleus accumbens  Microinfusions of an opioid agonist which is known to increase feeding and increased pleasure of food report o Depending where nucleus accumbens it was, got separation of map of nucleus accumbens and facial expression o Separation in reward system from bits that motivated desire to eat vs bits that provide (encode) pleasure from experience o Found that different parts did different things

Answer 336

o People were asked to smell vanilla odour or banana odour and rate their pleasantness o Then subjects ate a lot of bananas o Then were asked to rate the same smells again o Sensory specific satiety- satiety specific to thing eaten but some displeasure maintained to other things o Did the same with the scanner- found that orbital frontal cortex organises idea of pleasure and integrates that with motivation (even with placebo controls- vegetable boiled water rated differently on pleasure scale depending on whether told it was from a chef or just boiled water with vegetables)

Answer 337

• The OFC receives information from multiple sensory inputs (taste, smell, vision, somatosensory, gustatory etc) • Also has reciprocal connections to regions of the brain important for: o Reward and emotion (striatum, limbic system) o Behaviour selection and inhibition (dIPFC) • OFC is seen as a region important for linking reward to hedonic experience and then to motivation

Answer 338

• Yeomans et al. 2001 o Highly palatable foods disguise the effect of satiety o Told patients not to have breakfast when they came in o Gave them bland lunch (sandwiches) or roast beef rolls o Put tube down nose and into stomach and gave some preload (fat or carbohydrate) before their food o People with bland lunch and preload ate less bland lunch, for the others it didn’t matter

Answer 339

• Obesity o Unprocessed food leads to weight loss while ultra-processed food leads to weight gain, even if energy was the same o Eat more processed food o Large heritability quotient, but enabled by environment o Downregulation of susceptibility to internal satiety signals o Highly susceptible to external sensory cues, and to food palatability o Downregulation of dopamine o OFC and mPFC dysregulation o Hyperactivity in the learning system which associates cues with food to the reward pathways and increased activity in orbital frontal cortex and smaller prefrontal cortex impact o Similar thing to Volkow model will be happening when overweight

Answer 340

• Anorexia and bulimia o An obsessive disorder characterised by a vicious cycle of obsession about food and body image, starvation and hyperactivity o Relatively normal responses to peripheral satiety signals o Bulimia can respond to SSRIs (as does OCD) o People with anorexia showed decreased levels of noradrenergic metabolites and increased levels of serotonin o Both associated with changes in PFC and striatal activity

Answer 341

* Internal factors * Individual psychology of person * Physical activity (individual and environment) * Physiology * Food consumption and availability * Food production * Social psychology

Answer 342

• Women prefer men who are strong, masculine, kind, clever, ambitious and slightly older (who will have resources and can share them)

Answer 343

• Men prefer women who are youthful due to their possession of a specialised adaption called discounting the future, valuing immediate goods over future good

Answer 344

• Tool use is the use of an external object as a functional extension of mouth or beak, hand or claw, in the attainment of an immediate goal o Genuine tool- one that the animal manipulates  Associated with large relative neostriatum and entire brain o Borderline tools- objects that are used but not actually manipulated  Relates more to overall innovation rate but not to brain measures

Answer 345

• Intelligent animals such as chimpanzees can understand how to use the tool in novel situations, learning more than responses to cues, but don’t understand the concepts behind them (the why) o These types of animals can also choose appropriate tools for different situations  Using an object as a tool focuses attention on its functionally relevant features (so if trained with a blue cane which becomes useless it’ll pick a better can regardless of colour) or tool users may be predisposed to attend to such features • Intelligent behaviour in animals doesn’t arise spontaneously, but occurs with practice (some element of reinforcement but above instrumental learning) • Awareness of resurgence and automatic chaining may explain some tool use behaviours

Answer 346

* A quantitative trait locus is a section of DNA which correlates with variation of a quantitative trait in the phenotype of a population of organism * Quantitative trait loci usually underlie polygenic (continuous) traits rather than Mendelian traits

Answer 347

 Analysis of variance at the marker loci • ANOVA • T-test  Interval mapping • Most popular approach • Used to estimate the position of a QTL within two markers  Composite interval mapping • Performs interval mapping using a subset of marker loci as covarietes  Family-pedigree based mapping • Family based WTL mapping involves multiple families instead of a single family  Can make a manhattan plot- probability that variation in that part of the genome correlates with variation of a trait • Then check is specific genes in that region are driving variation

Answer 348

* Gene regulation- goal to increase or decrease the production of protein or RNA * Increases the versatility and adaptability of an organism by allowing the cell to express protein when needed

Answer 349

Results in increased expression

Answer 350

Results in decreased expression

Answer 351

 Determine whether or not gene is read into mRNA  Can be regulated by regulating RNA polymerase through: • Specificity factors, which alter the specificity of RNA polymerase for a given promoter • Repressors binding to the operator, blocking RNA polymerase • General transcriptions factors positioning RNA polymerase • Activators enhance the interaction between RNA polymerase and a particular promoter, encouraging gene expression  Enhancers- sites on the DNA that are bound by activators to loop DNA bringing promoters to initiation complex  Silences-regions of DNA sequences that, when bound by particular transcription factors, can silence expression of the gene

Answer 352

 Determine whether or not mRNA translated into a protein  Modulate (in eukaryotes): • Capping • Splicing • Addition of Poly(A) tail • Sequence-specific nuclear export rates • Sequestration of RNA transcript  3’ untranslated regions which contain binding sites(miRNA response elements) of miRNAs (when miRNAs bind to mREs, translation in inhibited) and regulatory proteins • miRNAs can be epigenetically altered  Altered by mRNA secondary structure, antisense RNA binding or protein binding  Some transcripts can self-regulate themselves

Answer 353

* DNA methylation can seemingly mediate dynamic variation in gene expression, whereas histone PTMs, however reversible, may subserve the sustained effects of experience on transcription. * Histone acetylation/deacetylation is transient and reliably associated with dynamic variation in transcriptional activity

Answer 354

• Familial studies: o High risk studies very expensive to conduct and a large sample size is needed • Environments are on a spectrum: not religious vs non religious doesn’t work like that

Answer 355

• Adoption studies o Adoptive parents are socioeconomically advantaged and have less mental problems due to adoptive screening o In adoption, certain parents will choose certain children (often on race and religion) o Allowed contact between biological parents and adoptive children

Answer 356

``` • The environment may: o Trigger a genetic predisposition o Compensate for a genetic predisposition o Enhance a genetic predisposition o Control a genetic predisposition ```

Answer 357

• Epigenetic changes, can be stable, reversible or dynamic

Answer 358

• Two models of gene-environment interactions: o Fan-shaped interactions, in which the influence of genotype is greater in one environmental context than in another o Crossover interactions, in which the same individuals who are most adversely affected by negative environments may also be those who are most likely to benefit from positive environments

Answer 359

o Passive gene-environment correlation refers to the fact that among biologically related relatives, parents provide not only their children’s genotypes but also their rearing environment

Answer 360

o Evocative gene-environment correlation refers to the idea that individuals’ genotypes influence the responses they receive from others

Answer 361

o Finally, active gene-environment correlation refers to the fact that an individual actively selects certain environments and takes away different things from their environment, and these processes are influenced by an individual’s genotype

Answer 362

• Autonomic nervous system o Involuntary system o Includes parasympathetic and sympathetic nervous system o Important for emotions

Answer 363

o Serotonin | o Acetylcholine

Answer 364

o GABA o Opioids o Gluococorticoids

Answer 365

• Major brain systems are activated by the stress sympathetic system and, in turn, influence its activity o Mesocortical dopamine systems  supplies prefrontal cortex responsible for anticipation and cognitive functions o Mesolimbic dopamine systems linked to nucleus accumbens, which plays principal role in motivational phenomena o Amygdala/hippocampus complex activated by noradrenergic neurons by brain stem or by emotional stressor  retrieves and emotionally analyses stressor information  Amygdala enhances stress response (CRF release) whilst hippocampus inhibits o CRH neurons in paraventricular nucleus lead to activation of proopiomelanocortin neurons that send projections to the paraventricular nucleus brain stem and other brain areas to counter-regulate CRH neuron and sympathetic system activity respectively, inducing analgesia and emotional tone

Answer 366

 Benzodiazepines (usually not used anymore- can be very addictive)  Buspirone (new)  Chlordiazepoxide Librium)  Diazepam (Valium)

Answer 367

- Amygdala - Fornix - Septal nuclei - Mammillary bodies - Anterior thalamus - Nucleus accumbens - Olfactory bulb - Hypothalamus

Answer 368

- Cingulate gyrus - Hippocampus - Parahippocampal cortices - Orbifrontal (ventral prefrontal) - Medial prefrontal cortices

Answer 369

* Connected with the frontal lobes, septal nuclei and the brain stem reticular formation via the medial forebrain bundle * Receives inputs from the hippocampus via the fornix and the amygdala via two pathways

Answer 370

The hypothalamus has centers involved in sexual function, endocrine function, behavioral function and autonomic control.

Answer 371

• The amygdala makes reciprocal connections with many brain regions including the thalamus, hypothalamus, septal nuclei, orbital frontal cortex, cingulate gyrus, hippocampus, parahippocampal gyrus and brain stem o Olfactory bulb ONLY area that makes input to amygdala but does not receive reciprocal projections

Answer 372

 Receives projections from the limbic system (thalamus, cerebral cortex and hippocampus) and olfactory bulb  The corticomedial nuclei projects to the hypothalamus via the stria terminalis, which from the hypothalamus projects to the HPA axis and the autonomic nervous system

Answer 373

o Connect to each other:  Lateral nucleus receives information from the temporal and frontal cortex • Appears to play an important role in acquisition and storage of memory associated with fear conditioning  Lateral nucleus sends projections to the basal and the accessory basal nucleus, as well as the central nucleus before they are sent to the brain stem and other areas of the brain – also send back to the frontal cortex and the cerebral cortex • Responsible for emotion changes, components of emotions (eg. Heart rate changes)  All nuclei project to central nucleus  Central nucleus connects to parts of the brain which generate emotional responses

Answer 374

 Plasticity in LA depends on calcium entry through NMDA receptors and voltage gated calcium channels  Elevated calcium triggers a number of intracellular cascades involving kinase mediated enzymatic reactions

Answer 375

o Learning during both fear conditioning and extinction requires NMDA receptor-dependent plasticity within the BLA

Answer 376

In the CNS

Answer 377

* Protoplasmic astrocytes- grey matter (neuronal cell bodies and synapses) * Fibrous astrocytes-white matter (neuronal axons)

Answer 378

o Glial chemical signals affect other cells  E.g. blood flow in brain responds to signals from astrocytes and glia  Glial cell calcium elevations stimulate the release of different gliotransmitters which regulate neuronal excitability and synaptic transmission • A single gliotransmitter may have different effects depending on the target neurons and neuronal elements • Glia respond to signals from neurons o The calcium-based cellular excitability displayed by astrocytes can be triggered by neuronal and synaptic activity through activation of neurotransmitter receptors expressed by glial cells • Much slower communication than neurons

Answer 379

• Greater intensities of electrical stimulation are needed to overcome the effects of drugs which block dopamine in the intracranial self-stimulation paradigm, and less stimulation is needed to produce the same effect with dopamine enhancers- dopaminergic drugs are affecting the intensity of reward and not behavioural performance

Answer 380

• Needed to replace electrodes due to their unprecise nature and drugs due to their slow acting effects

Answer 381

• Monoamine theory of depression- depression was the result of reduced neurotransmission of monoamines serotonin, noradrenaline and/or dopamine at synaptic sites in the brain o However, there are problems with this theory (e.g. effects of cocaine which is not an antidepressant yet blocks uptake of dopamine, serotonin and noradrenaline)

Answer 382

• Receptor sensitivity hypothesis- aetiology of depression may have a receptor basis, rather than being due to a deficiency of neurotransmitter release

Answer 383

• One explanation for the time lag of antidepressants is that continued exposure to the drug produce a gradual change in the functioning of the autoreceptors o The loss of inhibitory control by the autoreceptors causes the presynaptic neuron to gradually release more noradrenaline over the first few weeks of treatment

Answer 384

• Permissive hypothesis- low levels of serotonin permit abnormal levels of noradrenaline to produce either depression or mania o Low levels of serotonin will cause dysregulation of the noradrenergic system. o Therefore, antidepressant drugs are effective because they reinstate the ability of serotonin to control noradrenaline, thus restoring the critical balance that controls emotional behaviour o Thus, the stabilisation of one transmitter system by antidepressants may help restore the functioning of other ones

Answer 385

``` o Glucostatic (Mayer), lipostatic and aminostatic theories of hunger and satiety-  When brain detects a deficiency in one of these nutrients it causes hunger, and when levels are restored to a given point the result is satiety • Glucose deficiency- originally thought to be detected by glutates in hypothalamus but now thought to be detected by glucorceptors in the liver ```

Answer 386

• Neuropeptides o Small chains of amino acids which are released by various cells throughout gastrointestinal system o Act to suppress feeding, although a few increase food intake o Exert effect until they diffuse away from the synapse

Answer 387

``` Noradrenaline Orexins Growth hormone releasing hormone Galanin Neuropeptide Y Melanin-concentrating hormone Ghrelin Agouti-related peptide ```

Answer 388

``` Serotonin Dopamine Cholecystokinin (CKK) Corticrotropin-releasing factor Neurotensin Bombersin Gastrin-releasing factor Leptin ```

Answer 389

- Project to paraventricular nucleus and lateral hypothalamus - Produced by arcuate nucleus

Answer 390

-Receptors in paraventricular nucleus of hypothalamus and gastrointestinal tract

Answer 391

- Project to paraventricular nucleus and lateral hypothalamus - Produced by dorsomedial hypothalamus and arcuate nucleus - Most abundant neuropeptide and has enormous feeding response

Answer 392

Cholecystokinin (CKK) - Released by duodenum in presence of at or protein - Acts on stomach, gall bladder and pancreas gland - CCKa(gastrointestinal tract, stimulates vagus nerve which passes on satiety message to hypothalamus via nucleus of solitary tract) and CKKb receptors (in ventromedial hypothalamus and paraventricular nucleus)

Answer 393

Brainstem regions involved in feeding behaviour- • Nucleus of the solitary tract and adjacent area postrema- receives afferent information from the vagus nerve and relays input from the stomach, intestines, pancreas and liver • Dorsal motor nucleus of the vagus, which is the main source of vagal efferents innervating the gut and stomach • Brainstem contains regions which maintain the basic reflexes of satiety

Answer 394

* When the paraventricular nucleus is activated by neural or hormonal information signalling food intake, this acted to inhibit the lateral hypothalamus and satiation was the result * When the lateral hypothalamus was activated by signals specifying declining nutrient availability, this acted to inhibit the paraventricular nucleus, thereby causing hunger * However, this dual-centre model is not ideally demonstrated in lesions- effects wear off after a while

Answer 395

• Highly palatable foods are energy dense o Repeated carbohydrate and sugar ingestion act indirectly by affecting palatability and increasing insulin and glucose secretion. o The opioid neurotransmitter system then links the palatability or pleasure effects of food with the reward system. o Endogenous opioids subsequently trigger higher levels of dopamine release in the striatum, thereby reinforcing the consumption of food.

Answer 396

o Obesity develops when the energy intake of the body exceeds energy expenditure over time (usually many years), leading to the accumulation of excess fat tissue

Answer 397

 The nucleus accumbens is thought to be important in identifying stimulants by assessing reward and saliency (which is the feature of a thing that makes it stand out from all others).  The orbitofrontal cortex is involved in decision-making and determining the expected rewards and punishments of an action.  The amygdala and hippocampus are involved in forming memories of the stimulus/reward relationship, whilst inhibitory control and emotional regulation are provided by the prefrontal cortex and the anterior cingulate gyrus.  Addictive drugs and food, particularly in obese individuals, are believed to cause neurons from the ventral tegmental area to release the neurotransmitter dopamine in the nucleus accumbens.  These regions regulate activity in the frontal cortical regions. This pathway is referred to as the mesolimbic reward pathway  A person suffering from addiction, the reward pathway is disrupted such that the prefrontal cortex and cingulate gyrus are no longer controlling factors and compulsive behaviour is driven by the enhanced activation of the reward and saliency and memory and conditioning regions of the brain.  As such, when an individual is exposed to the reinforcing stimulant—drug or food—the system goes into overdrive.

Answer 398

• Lumley et al. o It is the process of sexual selection that protects and enhances fitness for individuals o Inbred beetles throughout generations and looked at 2 different forms of inbreeding  No sexual selection going on (remove choice for beetles) • Rapid extinction of population as line becomes infertile  Sexual selection going on (give beetle choice of mate) • Protects against inbreeding • Never go extinct

Answer 399

o Sexual selection protects against extinction and introduces variation required for evolutionary processes to occur if there is a change in environment

Answer 400

``` • Main factors in romantic relationships o Physical attractiveness o Propinquity  How frequently can come into contact with individuals o Familiarity o Similarity o Complementarity  Small amount of difference required o Reciprocal liking o Reinforcement ```

Answer 401

o Sexual desire  Chiefly associated with androgens (men) and oestrogens (women) o Romantic love  Dopaminergic and noradrenergic reward systems o Attachment  Oxytocin/vasopressin and its activity on dopamine system

Answer 402

• Styles of love o Eros: physical attraction, fleeting o Storge: Committed bonds, stable o Ludus: Played as a game, short term, deceptive o Pragma: There are benefits to being in a relationship o Mania: Obsessive love lived through a partner o Agape: Selfless love

Answer 403

Testosterone | Male sexual characteristics

Answer 404

Oestradiol | Female sexual characteristics

Answer 405

Progesterone | Uterine lining

Answer 406

GnRH | Stimulation of gonadotrophins

Answer 407

Lutenising Hormone Ovulation Follicle-stimulating Hormone Ovulation

Answer 408

Milk production, Male refractory periods

Answer 409

Lactation, orgasm, pair bonding (esp females)

Answer 410

Water retention, pair bonding (esp males)

Answer 411

• Sexual differentiation occurs at 6 weeks • SRY hormone only made by Y chromosome (which is absent in females) o If Y chromosome is activated, will make male gonads due to release of testis-determining factor by SRY gene  X or Y chromosome determines if either the Wolffian duct (male reproductive system) or Mullerian duct (female reproductive system) develop  Developed tests produce two hormones called testosterone and Mullerian-duct-inhibiting substance to develop Wolffian duct and inhibit formation of Mullerian duct  Lack of endocrine stimulation in females causses Wolffian system to degenerate and Mullerian duct to develop • Final stage of sexual development occurs in the brain where the testes and ovaries come under the control of the hypothalamus and pituitary gland

Answer 412

o However, pseudo-hermaphrodites (individuals who neither have completely male gonads or female gonads) can develop if abnormal hormonal release occur  They have a gonadal appearance opposite to their functionality

Answer 413

 Congenital adrenal hyperplasia in females- adrenal gland secretes androgens and they hence have a penis, but also have ovaries

Answer 414

 Androgen insensitivity syndrome in males- fail to produce a penis but also fail to produce a complete female reproductive system (e.g. vagina without uterus)

Answer 415

• Medial preoptic area (sexually dimorphic nuclei) in hypothalamus is different between the different genders o In males- cells in this part of hypothalamus is large  Testosterone within a critical peri-natal period causes enlargement of the SDN and changes the synaptic density of neurons o In females- smaller but more synapses than in the male one  Testosterone and its metabolite estradiol can masculinize female brains too o This sexually dimorphic nucleus organises sexual behaviour * Males have bigger brain due to androgen (testosterone) secretions * Men have a higher percentage of white matter whilst females have a higher percentage of grey matter * Men have bigger bed nucleus of the stria terminalis than men * Women have bigger splenium and anterior commissure than men * Men have a bigger inferior parietal lobe (for spatial and mathematic abilities) * Females have been shown to have larger areas of the brain associated with language * Two of the interstitial nuclei of the anterior hypothalamus (INAH-2 and INAH-3) are bigger in male brains than in females

Answer 416

``` • Initial phase-sexual attraction • Approach o Presenting and earwiggle from female • Appetitive behaviour (pre-sexual behaviour) o Genital investigation • Copulation o Mounting o Ejaculation (after one round of intromission) • Post-copulation o Intromission  Rat pulls away and licks himself after ejaculation o Separation ```

Answer 417

• Untreated male o Testosterone released at birth o When adult:  Tested with a male-does not have sex  Tested with a female- has sex • Untreated female o No testosterone released at birth o When adult:  Tested with a male- has sex  Tested with a female- does not have sex • Treated female o Treat female with testosterone at birth and when adult o When adult:  Tested with a male-does not have sex  Tested with a female- will try to have sex using male typical response • Castrated male o Deprived of testosterone at birth and given estradiol in adulthood o When adult:  Tested with a male- tries to have sex using female typical response  Tested with a female- will not have sex • Can change adult sexual behaviours of a rat by what is occurring at birth

Answer 418

• Epigenetic change at birth o Untreated female mice- epigenetic change occurs that inhibits female brain (through methylation) to keep SDN from becoming masculine o Testosterone will decrease this methylation of DNA in SDN and inhibit the inhibitory process, hence letting the brain become masculine o Therefore, through this system can change brain gender of animal regardless of gonads that animal has

Answer 419

• During development, sex hormones have an organisational effect on the animal that determines its gender and helps to organise the structure of the brain for later adult behaviour o Require a critical period in which to occur • Activational effects, where they stimulate certain behaviours

Answer 420

• The SDN and the male sex drive o Blocking the action of testosterone in the SDN affects male sexual behaviour  E.g. castration, testosterone antagonists, lesions  Blocks male copulatory behaviours  Can reduce sex drive too, but mainly in young animals, not older ones • Positive relationship between testosterone levels and aggression, and testosterone levels rise during success • Testosterone important determinant of spatial ability in a U-curve: in men, moderate levels of testosterone are best • High testosterone increases sperm count • Testosterone: o Have a higher ratio of 4th finger: 2nd finger  Higher ratio predicts risk-taking, predicts aggression o Males release testosterone constantly

Answer 421

• Effect of oestrogens controls a female’s willingness to mate (more oestrogen, more willingness) o During ovulation phase, most likely to initiate sex and in midluteal phase, least likely to initiate sex • Oestrogen released as a cycle (like the menstrual cycle) • Ventromedial hypothalamus- oestrogen in this region will increase receptiveness to males • Oestrogen promotes RNA synthesis which is believed to be important for increasing the number of progesterone receptors

Answer 422

``` • Menstrual cycle o Follicular phase  Eggs are being produced o Ovulation  Eggs released  Oestrogen released before ovulation and drops off when female gets progesterone (for fertility phase) o Luteal phase  Eggs are released into reproductive canal and menstruation occurs at the end of this phase ```

Answer 423

• Dopamine released during sex- conditioning yourself to the person you’re having sex with • During sex, the medial preoptic area further receives dopaminergic input from the medial forebrain bundle, which is likely to be involved in reward and reinforcement • Dopaminergic activity particularly linked to romantic love: o Strong “stimulus salience” effects o Rewarding effects of the feeling o Motivational aspects o Psychophysical aspects * Same system as addiction- symptoms such as jealousy are withdrawal effects * Important for motivating approaching behaviours * Brain areas that show activation in romantic love are the medial insula, anterior cingulate cortex, hippocampus, striatum, nucleus accumbens and hypothalamus (all high in dopamine concentrations)

Answer 424

o Show people images of people they love  Strong activation of ventral striatum system  Activation of ventral striatum not only romantic love  Show people of different people in scanner  Strong activation of the striatal nucleus and nucleus accumbens when shown pictures of romantic partner but not for friends or other types of acquaintances  Degree of activation correlated with how long people have been together • The longer, the stronger system is activated • Can predict how long people who’ve just begun dating are going to last

Answer 425

* Oxytocin and vasopressin strongly activate dopaminergic pathways in animals with long-term romantic partners such as prairie voles (although they often cheat on their partners) * In promiscuous animals (such as montane voles), not many oxytocin receptors in striatal pathways * Strong maternal bonds when breastfeeding comes from feedback system from oxytocin coming back into the brain and generating feelings of love * If unmated, if put oxytocin in brain of female vole, she will show strong preference towards rat about to be put in with her * If mated, strong preference between mates but if put in oxytocin antagonist, then that preference disappears in female vole * Same pattern of results for males but with vasopressin instead of oxytocin * Differences in behaviour must be induced by differences in V1a receptor distribution in the brain (dopamine and amygdala in prairie voles vs lateral septum in montane voles)

Answer 426

```  Classical endocrine responses o Oxytocin  Uterine contractions during labour, milk let down o Arginine vasopressin  Homeostatic effects on water retention in kidney  Both have major effects on: o Attachment and trust o Social cognition o Fear and anxiety o Pair-bonding and love ``` o Oxytocin and vasopressin are released after orgasm  Process by which people condition themselves to partners o Important for close maternal-child bonds o Intranasal sprays of oxytocin/vasopressin (depending on sex)  Increase trust in games  Reduces maternal separation anxiety  Increases memory for faces and speed of facial recognition  Reduces social anxiety

Answer 427

 Oxytocin receptors in the mesolimbic dopamine pathway: o OT increases nucleus accumbens dopamine o OT increases endogenous opioids  Dopamine induces release of oxytocin  Pro-social behaviour is related to oxytocin release

Answer 428

 Oxytocin and vasopressin produced by the paraventricular and supraoptic nuclei of the hypothalamus and are released into circulation by the pituitary gland

Answer 429

 Oxytocin decreases HPA axis activation whilst vasopressin increases it  Oxytocin decreases amygdala activity while vasopressin increases it

Answer 430

 Form social connections through imitation behaviours (which are not reinforced)  Try to understand other’s actions o Rizzolatti et al. discovered unusual activity of neurons in the pre-motor cortex of monkeys  Respond when planning to make an action  Also respond when watching another individual make a similar action  Mirror-neuron system: neurons active when individual does/feel thing themselves and when watch other people do it  People with psychopathy-reward pathways fire as well when they see people in pain  People who are on autism spectrum can’t interpret emotion from shapes

Neuroscience Flashcards

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