final exam Flashcards

Question

axon growthn & synapse formation; chemoaffinity hypothesis - pioneer growth cones vs fasciculation?

Answer 1

**Pioneer growth cones** - the first cones to travel along a particular route in the developing nervous system **Fasciculation-** the tendency for axons to grow along paths established by pioneer growth cones

Answer 2

Spatiotopic maps may have developed as a way to minimize the number of neural connections Point to point mapping of retina to tectum changes as the structures grow - Chemoaffinity is too simple to explain this phenomenon * *Topographical gradient hypothesis** - axons growing from one topographic surface to another are arranged according to the layout of the cell bodies on the original surface - This may be accomplished using signaling chemicals - E.g. ephrin A (medial-lateral) and ephrin B (dorsal-ventral)

Answer 3

Once axons have reached their target they must form an appropriate pattern of synapses (Require coordination between two different neurons) in order for a synapse to occur, both presynaptic and postsynaptic cell must agree upon (they need to have some acceptance of one another for that synapse to function) Synaptogenesis - the formation of new synapses, requires glial cells (astrocytes) -\> basically the creation of synapse but in order for those synapses to maintain themselves, they both need to function (requires coordination) * Retinal ganglion cells (in a culture) form 7x more synapses in the presence of astrocytes * Synapses quickly deteriorate when astrocytes are removed * Astrocytes: nutritional role?

Answer 4

what causes synaptogenesis? what promotes those neurons to agree to synapse with one another * Cholesterol provided by astrocytes * presence of astrocytes seems to be one of those promoters Neurons will synapse with any other neuron – promiscuous * they just want to synapse on everything / with any neuron * during prenatal development, there's way more synapse happening * once you're born you have 150% more synaptic connections that you need Inappropriate connections that don’t function will die off

Answer 5

neuron death is a normal part of the development * we want cells to go through cell death * this is a good thing because it allows other cells to create better/cleaner connections more neurons than are required (i.e., 50%) are produced * we also have too many neurons as well because we're born with 50% more neurons * after we're born we have to get rid of abt 50% of neurons and 150% of our neural connections (synapse) Many “waves” of neuron death occur during development

Answer 6

1. **apoptosis** (active): cells commit suicide, genetically programmed * this is within genetic programming 2. **necrosis** (passive): die from malnutrition

Answer 7

Apoptosis is safer, DNA and other structures are cleaved apart and packaged into membranes (majority of neuron death through development is from apoptosis) * Attracts scavenger microglia = phagocytosis * Problems with apoptosis can lead to cancers or neurodegenerative diseases Problems: Neurons that die usually have formed improper connections (cell that should have died, don't die which leads to a tumor) -\> when cells are supposed to die and they don't they create a mass (creating tumor) what if cell is pre programmed to die too son: you Membranes contain molecules to attract microglia Dark side – if apoptosis is blocked – cause cancer; if over-active – neurodegenerative disease (alzheimers, MS)

Answer 8

Neurons that fail to establish correct connections are particularly likely to die Space left after apoptosis is filled by sprouting axon terminals of surviving neurons Ultimately leads to increased selectivity of transmission ----- **Cells programmed for early death** – complete function and die Cells fail to obtain **life-preserving chemicals** that are supplied by targets – **neurotrophins – nerve growth factor**

Answer 9

More neurons are produced than needed by the adult brain - neuron cell death happens in waves at different parts of the brain and different time - this is a sign that the brain is mature / reac

Answer 10

**postnatal growth** is a consequence of: * •Synaptogenesis * Myelination – sensory areas and then motor areas. Myelination of prefrontal cortex continues into adolescence * Increased dendritic branches Overproduction of synapses may underlie the greater plasticity of the young brain

Answer 11

•The human brain quadruples in size between birth and adulthood (Not due to additional neurons) **Brain keeps growing until we are 2 years** – NOT due to more neurons **We have all the neurons we need by 7 months – 150% more synapses** - Exception - olfactory bulb and hippocampus

Answer 12

•Synaptogenesis occurs at different rates in different regions (Visual cortex vs. frontal cortex) **150%** more synapses by age 2 than adult Diff for diff brain areas – e.g. V1 prunes by age 3 – frontal cortex by puberty

Answer 13

•Myelination follows the pattern of functional development - Sensory regions, then motor regions, then higher-level areas Sensory within first few months Prefrontal cortex by early adulthood

Answer 14

•Dendritic branching progresses from deeper to more superficial layers of cortex Occurs even in adulthood Happens in seconds

Answer 15

the human prefrontal cortex has been linked to: 1. Working memory - maintaining relevant information to keep it accessible for short periods of time 2. Planning and sequencing actions 3. Inhibiting contextually inappropriate responses 4. Following rules for social behaviour

Answer 16

•Around 7-12 months of age, children tend to make a large number of **perseveration errors** - Inability to suppress the previous response when the task demands change Involves holding information in **working memory** about where to toy was placed AND being able to **supress that response** if toy placed in a different location.

Answer 17

•The Wisconsin card sorting test is typically used to assess frontal lobe function/dysfunction

Answer 18

**Critical period** - when it is absolutely essential for an experience to occur during a particular interval **Sensitive period** - when the experience has a great effect on development at a certain interval, but can still have effects outside of the interval

Answer 19

•Rats raised in the dark had fewer synapses in visual cortex - Had problems with depth and pattern vision as adults •Rats raised in “enriching” environments solved mazes faster than rats raised in non-enriched environments (Hebb, 1947)

Answer 20

•**Antonini & Stryker (1993)** – found that a few days of monocular deprivation produced a massive decrease in axonal branching from the sensory layer in V1

Answer 21

* Roe (1990) - altered the course of developing retinal ganglion cell projections to the MGN * Neurons in auditory cortex acquired a retinotopic map!

Answer 22

•Knudsen and Brainerd (1991) - raised barn owls with prisms that shifted their vision in one direction (e.g., 20° to the right) oAuditory spatial maps were realigned to match the visual map

Answer 23

•Munte et al. (2002) - early music training enlarges the size of auditory cortex that responds to complex musical tones

Answer 24

* Neurogenesis – the growth of new neurons * Nottebohm et al. (1983) found brain structures involved in singing increased before each mating season -- * Most researchers believed that neurons could not be regenerated in adulthood * In the 1990’s researchers observed two important findings 1. New neurons are continually added to the olfactory bulbs in rats 2. New hippocampal neurons are continually added in primates

Answer 25

* Tinnitus (ringing in the ears) – produces major reorganization of primary auditory cortex * Adult musicians who play instruments fingered by left hand have an enlarged representation of the hand in S1 Skill training leads to reorganization of motor cortex

Answer 26

* Much of what we know about normal development has emerged from studying cases where development is abnormal * **Autism** is a complex developmental disorder that appears before age 3 - A reduced ability to interpret the emotions of others - Reduced capacity for social interaction and communication - Preoccupation with a single object or activity - Autism is a spectrum disorder o80% are male o50% have mental retardation o35% have seizures oOlder parents (mothers over 30, fathers over 40)?

Answer 27

•Early indicators of autism: • 1.Delayed language development •no meaningful phrases by 24 months 2.Delayed development of social interaction •no happy expressions by 9 months, no communicative gestures by 12 months

Answer 28

•Autism is one of the most prevalent childhood neurological disorders o1990’s \< 1 in 1000 births oRecent estimates are 1 in 88! oBroadening diagnostic criteria? oIncreased public awareness?

Answer 29

•Autism is a heterogeneous disorder - Some individuals with autism are severely impaired in some skills, but excel rapidly at others •**Autistic savants** - are individual with autism who display incredible abilities in certain areas oArtists / Musicians / Mathematical abilities

Answer 30

* Because the disorder is so heterogeneous it is hard to pin down any underlying neural abnormalities * One characteristic of autism that has received considerable attention is their lack of social interaction - Look less at faces and disinterested in making eye contact - Abnormal FFA activity in individuals with autism

Answer 31

* Occurs in 1 in 7500 births * Is a neurodevelopmental disorder characterized by: - Near normal language abilities - Normal or superior musical abilities - Very emotionally expressive and socially interactive (hypersociability

Answer 32

•Is a neurodevelopmental disorder characterized by: oMental retardation (IQ below 60) oSevere visuospatial problems - Spatial memory / Drawing oGenetic basis - Abnormalities on chromosome 7 oCortical thinning - Parietal-occipital junction / Orbital-frontal cortex oCortical thickening - Primary and secondary auditory corticles

Answer 33

•Many potential sources of brain injury: 1. Tumors 2. Cerebrovascular disorders 3. Closed head injuries 4. CNS infections 5. Neurotoxins 6) Genetic influences

Answer 34

•A **tumor** or neoplasm- a mass of cells that grows independently of the rest of the body oApproximately 20% of tumors in the CNS ar**e meningiomas** oMeningiomas are encapsulated oExert pressure on surrounding tissue (mass occupying) oMost are benign (i.e., non-cancerous --- Grow between meninges that protect the brain Exception rather than rule

Answer 35

•Most brain tumors are **infiltrating tumors** oNot encapsulated and grow diffusely throughout the brain oMost are malignant (i.e., cancerous) o10% of tumors are **metastatic**; originate in another part of the body and are transferred via the bloodstream

Answer 36

•Strokes- a sudden interruption in blood supply to the brain that results in brain damage oLeading cause of brain damage and adult neurological disability oSymptoms depend on brain region affected o**Common outcomes:** memory loss, aphasia, paralysis, vision loss o**Signs of stroke onset**: weakness, trouble speaking, vision problems, headache, dizziness

Answer 37

Dead brain tissue resulting from a stroke is called an **infarct** “At risk” tissue surrounding the infarct is called the **penumbra** Most interventions aim to minimize the penumbra

Answer 38

1) cerebral ischemia: is a disruption of blood supply caused by a blockage in a blood vessel 2) cerebral hemorrhage: •when a blood vessel ruptures and blood seeps into surrounding tissue causing damage

Answer 39

* Cerebral hemorrhage- when a blood vessel ruptures and blood seeps into surrounding tissue causing damage * Aneurysm- a balloon like swelling in an artery - Caused by defective elasticity in an artery - Can be congenital- arteriovenuousmalformation(AVM) oCerebral angiogram

Answer 40

•**Cerebral ischemia**- is a disruption of blood supply caused by a blockage in a blood vessel o**Thrombosis**- plug formed in a vessel (blood clot, fat, tumor cells, air bubble, oil, etc.) •Tissue plasminogen activator (tPA) o**Embolism-** a plug that forms in a larger vessel that travels to a smaller vessel - Transient ischemic attack (TIA) **arteriosclerosis**- narrowing of blood vessels because of fat deposits

Answer 41

* **Ischemia-induced brain damage:** * takes time * does not occur equally in all parts of the brain * mechanisms of damage vary with the brain structure affected

Answer 42

**1) closed head injuries**: injuries (CHI)- are any blow to the head that does not penetrate the skull leading to brain injury 2) **Contusion**- any CHI that involves damage to brain’s circulatory system oBrain slams against the inside of the skull causing damage

Answer 43

* Build-up of clotted blood (bruise) in brain tissue following a contusion * Causes pressure on underlying brain tissue

Answer 44

•A general term for cognitive disturbances following a closed head injury where there is no evidence of a contusion or other brain damage oLoss of consciousness oEffects of multiple concussions **- “Punch-drunk syndrome”** **---** Damage from concussion can usually be seen only on autopsies of brains from cadavers. •The brain of John Grimsley and the boxer show large amounts of abnormal tau protein in the amygdala

Answer 45

* When bacteria infect the brain they commonly lead to the formation of **cerebral abscesses** / i.e., pockets of puss in the brain * **Meningitis** is caused by bacterial infection (25% of adult cases are fatal) * **Syphilis** bacteria also leads to severe brain damage / STD passed through genital sores, can be dormant for years **General paresis** – the syndrome of insanity/dementia that results from syphilitic infections of the brain

Answer 46

•**Rabies virus**- transmitted via a bite from an infected animal (e.g., bats, cats, raccoons, dogs, mice) oHas an affinity for the nervous system oVirus attacks the brain about 1 month after the bite oExtreme aggressiveness oUsually fatal if not treated ---- •Mumps & Herpes virus can also attack the brain **oHerpes encephalitis** Attacks all tissue, including brain

Answer 47

•The nervous system can be damaged through the intake of a variety of chemicals oLead (“crackpot”) oMercury (“mad hatter”) oPesticides and farming chemicals? • •Toxic psychosis- chronic insanity produced by a neurotoxin (**Tardive dyskinesia (TD)** )

Answer 48

the characteristic feature of epilepsy is seizures (spontaneous / reoccurring) •People with epilepsy (1% of population) have chronic seizures caused by underlying brain abnormalities oMany different subtypes depending on nature of seizures 1. **Partial seizures**- involve only part of the brain 2. **Generalized seizures**- involve the entire brain (**Epileptic auras**- psychological changes that occur prior to a seizure) --- * Many different causes - i.e., brain damage,toxins, viruses, tumors, genetics * Many cases are due to improper inhibitory synapses

Answer 49

note: Not all seizures are due to epilepsy (Neurotoxins and Febrile seizures) •Epilepsy diagnosis relies heavily on EEG recordings - Sudden onset of high amplitude EEG waves

Answer 50

**Partial** – does not involve the entire brain **Generalized** – involves the entire brain --- note (Partial) Not usually associated with a loss of consciousness Patient remains alert and can remember the experience

Answer 51

1) **Simple partial seizures** – symptoms are primarily sensory or motor or Short lasting (less than a few minutes) Symptoms depend on where in the brain the seizure originates from 2) C**omplex partial seizures** – patients engage in compulsive, repetitive, simple behaviours (automatisms) and more complex behaviours can appear perfectly normal Usually restricted to the temporal lobes During an episode the patient engages in compulsive repetitive behaviours E.g., repetitive mouth movements, buttoning and unbuttoning a shirt, walking, driving Patient appears conscious but memory loss for the event is common About 50% of adults cases of epilepsy are complex partial

Answer 52

1) **Petit Mal** - no convulsion. The primary symptom is the petit mal abscense (disruption of consciousness, cessation of ongoing behaviour, vacant look, fluttering eyelids) Petit mal seizure- “little trouble” - No convulsions Petit mal absence- disruption of consciousness, cessation of behaviour, vacant look, “day dreaming” More common in children 2) **Grand Mal** - Loss of consciousness, loss of equilibrium, violent tonic-clonic convulsion. Tongue-biting, urination, and cyanosis are also common. Grand mal seizure- “big trouble”/ loss of consciousness / violent tonic-clonic convulsions **Cyanosis**- turning blue from excessive extraction of oxygen from the blood **Hypoxia** can occur resulting in further brain damage

Answer 53

* A progressive disease that destroys myelin in the CNS * Typically onsets in early adulthood * Starts with microscopic damage, later leads to axon degeneration * MS is an **autoimmune disorder** * Periods of remission for up to 2 years Causes a variety of symptoms: oVisual disturbances / Muscular weakness / Ataxia (loss of motor coordination) / Cognitive deficits

Answer 54

**Genetic factors in MS** oHigher concordance rate in monozygotic (25%) vs. dizygotic (5%) twins o3 x higher rate of MS in females compared to males oMuch higher rates in Caucasians (0.15%) than other ethnic groups **Environmental factors in MS** oHigher rates in populations living in colder climates (distance from equator), vitamin D oRisk of developing MS changes with migration between climates oSmokers are at greater risk for developing MS --- notes: Highest rates in Canada are here in Alberta Also those exposed to the Epstein-Barr virus – common cause of Mono.

Answer 55

* The most common cause of adult **dementia** * Terminal **progressiv**e neurodegenerative disease o_Early stages_- decline in memory functions, attention problems, personality changes o_Intermediate stages_- confusion, irritability, anxiety, deterioration of speech o_Advanced stages_- lose control over bodily functions -- Can occur in 40s-50’s 10% of people over age 65 35% incidence in people over age 85

Answer 56

•**Neurofibrillary tangles-** are tangles of protein in the neural cytoplasm oDestroys microtubules / Tau protein -- •A**myloid plaques**- clumps of scar tissue made up from dying neurons and beta amyloid protein

Answer 57

* Alzheimer’s disease destroys association cortex * Distribution of plaques and tangles in AD

Answer 58

•Finding an effective treatment rests on finding the primary symptom oPlaques or tangles? oPrevention is key! •Treatments for Alzheimer’s Disease oAll 3 genes implicated in early onset AD influence amyloid production oAmyloid vaccine? oAcetylcholine? Deep brain stimulation? ---- AD has a major genetic component - People who have AD in their family have a 50% chance of getting the disease in their 80’s Genetic component of AD is complex - 3 specific genes in early onset AD (age 40) - Over 20 chromosomes implicated in late onset AD - Suggests AD is due to epigenetic mechanisms

Answer 59

* Comprised of 3 nuclei: caudate, putamen, globus pallidus * Receives input from most areas of cortex * Plays a critical role in modulating the force of movements * Also plays an important role in motor learning

Answer 60

* Results from death of dopamine (D) secreting cells in the substantia nigra * Absence of D results in not enough inhibition of the GPi in the direct pathway and too much excitation of the GPi in the indirect pathway * Characterized by: oMuscular rigidity / Hypokinesia (loss of movement) /Resting tremor /Cognitive impairments --- Deep brain stimulation inhibits STN (subthalamic nucleus) STN = subthalamic nucleus

Answer 61

* Animals models offer the unique opportunity to understand the ultimate causes of neurological diseases * Animals models help with the development of treatments * Not perfect!

Answer 62

* A series of periodic brain stimulations eventually elicits convulsions: **the kindling phenomenon** * Neural changes are permanent * Produced by stimulation distributed over time * Convulsions are similar to those seen in some forms of human epilepsy – but they only occur spontaneously if kindled for a very long time * Kindling phenomenon is comparable to the development of epilepsy (epileptogenesis) seen following a head injury

Answer 63

* Only humans and a few related primates develop amyloid plaques * Transgenic – genes of another species have been introduced * Genes accelerating human amyloid synthesis introduced in mice oPlaque distribution comparable to that in AD oUnlike humans, no neurofibrillary tangles

Answer 64

* In 1982 small group of drug users each reported to a local emergency room with sudden onset of Parkinson’s symptoms (Awakening the frozen addicts) * Each had used a new type of synthetic heroin * Later analysis revealed that the heroin contained a neurotoxin- MPTP was selectively toxic to dopamine

Answer 65

* When MPTP is administered to monkeys it creates Parkinson’s Disease like symptoms * Leads to major cell loss in the substantia nigra * Research using the MPTP model discovered that Deprenylblocks the effects of MPTP

Answer 66

•A common way to study **neural degeneration** is to cut the axons of neurons (axotomy) and observe the effects --- two types of degeneration occur: 1) anterograde degeneration 2) retgrograde degeneration

Answer 67

1.Anterograde degeneration- is the degeneration of the distal segment, i.e., between the cut portion and the terminals –Occurs quickly over a few hours

Answer 68

2.Retrograde degeneration- degeneration of the segment between the cut portion and the cell body * Occurs slowly over a few days * Decrease in cell body size suggests cell will die * Increase in cell body size suggests cell will attempt to replace the cut segment

Answer 69

•Transneuronal degeneration - Sometimes damage spreads from damaged neurons to neurons within the network oAnterograde – spreads from damaged neuron to the neuron it synapses with oRetrograde – spreads from damaged neuron to the neuron that synapses on it

Answer 70

* Does not proceed successfully in mammals and other higher vertebrates – capacity for accurate axonal growth is lost in maturity * Regeneration is virtually nonexistent in the CNS of adult mammals and unlikely, but possible, in the PNS

Answer 71

* PNS neurons can regenerate starting 2-3 days after injury * Recovery depends on the nature of the injury * Schwann cells clear debris and promote regeneration - Produce neurotrophic factors and cell-adhesion molecules --- Regeneration depends on the environment – not necessarily the neurons (CNS vs PNS)

Answer 72

* **Oligodendroglia** (myelinate CNS neurons) do not clear debris, or guide and stimulate regeneration * Instead, they release factors that actively block regeneration!

Answer 73

* Collateral sprouting- axon branches can sprout from nodes of Ranvier to connect to adjacent neurons * more accurate in invertebrates than vertebrates When they lose a limb, the regenerating axons produce a growth factor that promotes regeneration of the limb

Answer 74

Pons and colleagues (1991)- mapped S1 in monkeys whose contralateral arm sensory neurons had been cut 10 years prior oFound that the cortical face representation had expanded into the former hand region

Answer 75

* Sanes, Suner, and Donoghue (1990) * Transected motor neurons that controlled the muscles of rat whiskers * A few weeks later, the area of the motor cortex that had previous elicited movement of the whickers now activated other muscles of the face

Answer 76

•Brain-imaging studies indicate there is continuous competition for cortical space by functional circuits oe.g. Auditory and somatosensory input may be processed in formerly visual areas in blinded individuals

Answer 77

•Two mechanisms might explain the reorganization of neural circuits: 1) S**trengthening of existing connections through the release from inhibition** * Recovery often happens very quickly * Change is never greater than 2mm of cortex 2) **Establishment of new connections via collateral sprouting** •Long term recovery can be too dramatic to be explained by small changes in existing circuits note: These two mechanisms may work together Other possibilities: dendritic branching, neural degeneration, and adult neurogenesis

Answer 78

•Hard to study because of other compensatory changes, for example: oCerebral edema (brain swelling) decreases a week or two after damage olearning of new cognitive or behavioural strategies oCognitive reserve (education and intelligence) can also play a role in helping patients accomplish tasks in alternate ways -- Most likely the case when: lesions are small and patient is young Kapur (1997) – examined doctors and neuroscientists with brain damage who had great recovery – not due to recovered brain function but strategy Might also be why educated people are less susceptible to age-related brain deterioration

Answer 79

* There is a lot of interest in finding out whether adult neurogenesis could contribute to recovery * Stem cells tend to migrate short distances following brain damage * E.g., increase in neurogenesis in dentate gyrus following ischemia damage --- No evidence that stem cells migrate from their sites of generation

Answer 80

•Younger people recover better over the long run!

Answer 81

1) reducing braind damage by blocking neurodegeneration 2) promoting regeneration 3) neuro-transplantation

Answer 82

* Various neurochemicals can block or limit neurodegeneration * Neuroprotective molecules tend to also promote regeneration -- Estrogen – may be why brain disorders are more common in men - Seen to protect the brain in brain damage (found mostly in women) This is stopping cell suicide (usually happens in stroke) Can we produce nerve growth factors? -Maybe iy can create an environment that is more regenerative

Answer 83

•Researchers induced cerebral ischemia in groups of rats o**Control group** - damage to the hippocampus and poor performance in the Morris water maze o**Experimental group** - treated with a virus that was engineered to release an apoptosis inhibitor protein oRats in the experimental group had less hippocampal damage and performed better in the Morris water maze task --

Answer 84

* CNS regeneration does not normally occur in mammals * But can be induced in lab animals * Cheng et al. (1996) severed the spinal cord of rats making them paraplegic oTransplanted sections of myelinated peripheral nerves into the spinal cord oSpinal cord regenerated through the myelin sheaths of the implanted Schwann cells oRats regained movement of legs

Answer 85

•Fetal tissue transplants have been used to treat Parkinson’s Disease in some animals and humans oTreatment was successful oLimited success with humans --- PD – lack domapine-releasing cells Could stem cells implanted do that job? It was first on the list but now last - Reseracrhechs worked mainly on Parkinsons - They believed that if they can take stem cells, they could become anything and then they transplant it to the substantial nigra - It was working (regaining some function) and about 3 weeks or so it stopped working - They stopped the research because they didn’t take they have enough research abt the environment

Answer 86

•Neural stem cells have been used to repair spinal cord injuries in rats (McDonald et al. 1999) - Injected embryonic stem cells migrate to the area of injury and develop into new nerve cells - Paraplegic rats regained ability to support weight with legs and walk •More research is needed to maximize the survival and growth of neurons oNeurons need to mature and make proper connections to enhance recovery oMethods for keeping new neurons healthy still need to be developed

Answer 87

•Facilitated walking as an approach to treating spinal injury (90% of trained walkers – only 50% using conventional rehab) epidural stimulation -

Answer 88

* Rodents raised in enriched environments are resistant to induced neurological conditions (epilepsy, models of Alzheimer’s, Huntington’s, etc.) * Physical activity promotes adult neurogenesis in rodent hippocampus Wheel-running increases neurogenesis in hippocampus of rats Also reduced growth of amyloid plaques in models of AD

Answer 89

Learning and memory are two sides of the same coin **Learning** – how the experience changes the brain **Memory** – how these changes are stored and reactivated If we couldn’t learn or remember, we would be frozen in the present

Answer 90

* Amnesia- loss of memory, usually as a result of brain injury * Anterograde amnesia is typically accompanied by some degree of retrograde amnesia

Answer 91

HM (1926-2008) had severe epilepsy and drugs could not prevent his seizures * At age 27, Dr. Scoville performed a bilateral temporal lobe resection to treat his epilepsy (1953) * Following the surgery his seizures were dramatically reduced * He had some retrograde amnesia for events shortly before the surgery oCould remember his childhood and everything about 2 years prior to the surgery * He had a normal IQ and a normal short-term memory post-surgery * However, H.M. presented with a profound anterograde amnesia - He could not remember people he met since his surgery - He could read the same jokes and stories over and over again

Answer 92

Short-term memory-immediate memory, limited capacity Long-term memory-memory for past events, unlimited capacity Consolidation- the process of converting short-term memories into long-term memories

Answer 93

1. The hippocampus is not the location of long-term memories 2. The hippocampus is not the location of short-term memories 3. The hippocampus is involved in converting short-term memories into long-term memories (consolidation) -- •Following his surgery HM had normal short-term memory oDigit span •HM also demonstrated other remarkable spared abilities oMotor learning (mirror drawing, rotary pursuit) oPerceptual learning (incomplete pictures test) oPavlovian (classical) conditioning

Answer 94

The picture is viewed through a mirror so the image is reversed After a few trials people get better at copying the picture When tested after a delay people typically show retention HM showed retention over several days- but never remembered doing the task!

Answer 95

HM’s ability to recognize broken line drawings improved over subsequent testing sessions HM insisted that he had never seen the pictures before

Answer 96

•H.M. was able to acquire a classically conditioned eye-blink response oHe still showed retention 2 years later

Answer 97

Why two parallel memory systems??? Implicit is simple, doesn’t involved consciousness Explicit allows for flexibility in using that learned knowledge in a different context

Answer 98

•Two different types of explicit memories: o**Semantic memory**- are explicit memories of factual information o**Episodic memory**- are explicit memories for specific events (i.e., episodes) * Many amnesics (other than HM) can acquire new semantic memories but fail at tests of episodic memory * Temporal lobe amnesia seems to be a specific disorder of episodic memory

Answer 99

* Damage to medial temporal lobes via a motorcycle accident * General intelligence and language normal * Semantic memory intact * Severe amnesia for personal experiences (autobiographical memory) * Cannot imagine himself in the past or future – “time travel” -- Knows facts of early life – birth date, where he lived, summer cottage was located, names of schools attended, etc Difficult to spot these episodic deficits because we don’t have knowledge of one’s personal past

Answer 100

* Patient R.B. (52 year old male) suffered a heart attack and subsequent anoxia (loss of oxygen = stroke) * Although he was revived he suffered permanent anterograde amnesia * Autopsy revealed selective damage to the CA1 field of the hippocampus

Answer 101

•AD causes widespread degeneration of association cortex including the medial temporal lobe oAnterograde + retrograde amnesia oShort term + implicit memory also affected •There is also degeneration of the basal forebrain which generates acetylcholine oAChE inhibitors

Answer 102

* Concussions often result in a loss of consciousness * Many individuals will experience amnesia for events immediately preceding and following the concussion

Answer 103

* Concussions disrupt consolidation (storage) of recent memories * **Hebb’s theory** – memories are stored in the short term by neural activity * Interference with this activity prevents memory consolidation Examples: oBlows to the head (i.e., concussion) oECS (electroconvulsive shock)

Answer 104

* Electroconvulsive Shock (ECS) – an intense, brief, diffuse, seizure inducing current that is administered to the brain through large electrodes * Shock disrupts consolidation * The length of the retrograde amnesia could give an estimate to how long consolidation takes

Answer 105

* Thirsty rats learned where the water bottle was in a box cage * Then 10 secs, 1 min., 10 mins., 1 hr., 3 hrs. later the rat would receive ECS Consolidation took between 10mins and 1 hour

Answer 106

* HM’s case study was the first to indicate that the hippocampus was critical for forming new memories * Researchers attempted to create an animal model of amnesia to better understand the underlying anatomy * Early attempts at creating an animal model were unsuccessful o**Researchers were overly focused on the hippocampus** (What about the amygdala + rhinal cortex?) oH**ad difficulty demonstrating memory deficits in animals with hippocampal lesions** (Using the wrong memory tests?) --- Animals mostly tested for explicit memory

Answer 107

Delay non-match to sample (DNMS) task

Answer 108

* “Normal” monkeys perform the DNMS task correctly on 90% of trials * Monkeys with medial temporal lesions perform worse as the delay interval increases

Answer 109

Is it really damage to the hippocampus that causes amnesia? Much of the input to the hippocampus from the cortex must go through the rhinal cortex! -- R.B. had damage to CA1 subfield – ischemia-induced hyperactivity damaged regions outside the hippocampus

Answer 110

Subsequent studies in rats found that damage to the rhinal cortex led to amnesia NOT the hippocampus R.B. had damage to CA1 subfield – ischemia-induced hyperactivity damaged regions outside the hippocampus

Answer 111

* Subsequent studies have shown that the hippocampus plays a critical role in spatial memory * Rats with hippocampal lesions perform poorly on both the Morris water maze, as well as the radial arm maze

Answer 112

•Specific cells in the hippocampus respond only when the animal is in a particular location in space oReflects where the animal thinks it is in space oThis map is created in the hippocampus through learning * Found mostly in the dorsal (posterior) hippocampus in pyramidal cells in the CA1 field * Rhinal cortex has “grid neurons”

Answer 113

* Black-capped chickadees show an increase in the size of the hippocampus during late fall * London taxi drivers were found to have larger posterior hippocampal volumes (Maguire et al., 2000)

Answer 114

* Each memory is stored diffusely throughout the brain structures that were involved in its formation. * Some structures have particular roles in storage of memories. o**Hippocampus:** spatial location o**Perirhinal cortex:** object recognition o**Mediodorsal nucleus:** Korsakoff’s symptoms o**Basal forebrain:** Alzheimer’s symptoms -----

Answer 115

**5 other memory areas:** 1. Medial-temporal cortex 2. Amygdala- fear conditioning; strengthening of emotional memories 3. Prefrontal cortex- temporal sequences of episodic memory; working memory 4. Cerebellum - classical conditioning; habit formation 5. Striatum - classical conditioning; habit formation

Answer 116

•Hebb’s rule - if a synapse becomes active repeatedly at the same time that the post-synaptic neuron fires the synapse will be strengthened Efficiency in synaptic transmission was the basis for long-term memory

Answer 117

Neurons within the hippocampus appears to follow Hebb’s rule!

Answer 118

LTD-long term depression can also occur following low frequency stimulation (\<10Hz) •Two key properties link LTP to learning: (1) Can last a long time (2) Only occurs in BOTH sending and receiving neurons are firing – called **co-occurance**

Answer 119

When a strong stimulus is paired with a weak one, their connection becomes strengthened

Answer 120

* Rapid stimulation causes the EPSPs to summate which depolarizes the postsynaptic membrane * LTP requires 2 events: 1. Activation of pre- synaptic neuron 2. Depolarization of the postsynaptic neuron

Answer 121

* Found mostly in the CA1 subfield * Controls a calcium ion channel which is normally blocked by a magnesium (MG2+) ion * If postsynaptic membrane is depolarized the MG2+ ion is ejected, and Ca2+ enters * Glutamate must also be present

Answer 122

* NMDA receptors are active **ONLY** when glutamate is present and when the postsynaptic membrane is depolarized * NMDA receptors are both NT **and** voltage dependent * Blockage of NMDA receptors with AP5 _prevents LTP_ * AP5 does not interfere with LTP that has already been established

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Allows neural networks to learn associations

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* The strengthening of synapses relates to an increase in postsynaptic AMPA receptors * AMPA receptors are glutamate receptors that control Na+ channels * The creation of new AMPA receptors increases the postsynaptic response to glutamate -- Maintanence of LTP - memory

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* After Ca2+ enters the postsynaptic dendrites it activates CaM-KII, a protein kinase * CaM-KII then delivers AMPA receptors to the membrane via vesicles

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Dendritic spine splits active zone Each active zone grows

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•Presynaptic changes can also occur following LTP oe.g., Increase release of glutamate release * Presynaptic changes may be related to the activation of nitric oxide (NO) * NO can act as a presynaptic messenger

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Glutamate released and binds to NMDA receptor Calcium enters and activates CaMKII which causes insertion of AMP receptors LTP also causes perforated synapses or new ones Calcium activates NO which diffuses out and back into terminal button to increase glutatmate release

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•All mammals and birds sleep (need REM) • •We spend about 1/3 of our life sleeping • * Sleep deprivation can disrupt cognitive functions and has a profound effect on mood (irritability) * One good nights sleep can make up for days of deprivation Boy who went 264 hours without sleep – Guinness Record oAfter this ordeal he slept for 15 hours 1st night, 10 hrssecond and 9 hrs 3rd oOnly 7% of stage 1 and 2 made up, but 68% of stage 4 and 53% of REM were made up

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•Recuperation theories oSleep is needed to restore homeostasis oWakefulness causes a deviation from homeostasis

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•Adaptation theories oSleep is the result of an internal timing mechanism oSleep evolved to protect us from the dangers of the night

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•Attach electrodes to scalp to measure brain waves while sleeping

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Sleep spindles – we get it every few minutes / mask outside noises K complexes –

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* Two basic patters: **alpha and beta** * Alpha consist of regular, medium frequency (8-12 Hz) waves * Usually occurs when eyes are closed and in a relaxed state * Beta waves are irregular and lower amplitude (13-30 Hz) * Shows asynchrony due to multiple neural circuits at work

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* Theta Waves (3.5-7.5 Hz) * Usually transition between sleep and wakefulness * EOG show rolling eye movements * Stage lasts for about 10 minutes * If awoken, people will often claim that they were “thinking”

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* Mixed frequencies with occasional bursts of 12-14 cps * **Sleep spindles** may be the mechanism that decreases the brains sensitivity to sensory input - Found throughout stages 1-4. * Older people have fewer sleep spindles - more awakenings * **K complexes** only found during stage 2 - Can be triggered by noises

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* Stages 3 and 4 - High amplitude **Delta waves** (\>3.5 Hz) * Deepest stage of sleep - if woken, will be groggy and confused

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* Paradoxical sleep because brain is awake but body is asleep * If awoken during REM, person will be alert and attentive * They will invariably report that they were dreaming * Complete muscle atonia - prevents us from acting out our dreams * Erections in males, increased vaginal blood flow in females - not related to content of dreams. --

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* 90 min cycle * 4-5 periods of REM sleep * Each period is about 30 min long * Refractory period following REM -- Deep sleep (3 & 4) – ure body is at rest During ren sleep ur body is sleeping but ur brain is active

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•It is difficult, if not impossible, to separate the effects of **stressors** used to prevent sleep from the effects of lost sleep

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•**3-4 hours of deprivation in one night** oIncreased sleepiness oDisturbances displayed on written tests of mood oPoor performance on tests of vigilance • •**2-3 days of continuous deprivation** oExperience microsleeps, naps of 2-3 seconds oUpdating plans and strategies oInnovative, lateral, insightful thinking oReference memory

Answer 142

* After sleep deprivation, most of lost stage 4 is regained and SWS is increased * Short sleepers get as much SWS as long sleepers * Naps without SWS do not decrease the night’s sleep * Gradual reductions in sleep time lead to decreases in stages 1 and 2 * Little sleepiness produced with repeated REM awakenings, unlike SWS -- Short sleepers and long sleepers get the same quality of sleeo 20-30 mins (ure not tajing that sleep wave or rem sleeo so ull still be able to sleep at night)

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•Two consistent effects oProceed more rapidly into REM as REM deprivation increases oREM rebound – more time spent in REM when deprivation is over •REM rebound suggests that REM sleep serves a special function -- We can wake u up during rem sleep -\> eeg or They experience more rem sleep if the day before if they get woken up during their REM stage Our brain needs it (don’t rlly know what that function is yet)

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•**Promotes learning** oDevelopmental evidence * REM duration peaks at most active stage of development * 70% of newborn’s sleep is REM * 6mths - 30%, 8yrs - 22% and adulthood - 15% * Could be determined by the fact that REM is necessary for development OR REM increases with learning

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•Processing of explicit memories? oInconsistent findings oAntidepressant REM-blocking drugs do not interfere with memory •**Default theory:** it is difficult to remain in NREM sleep (essentially, rem sleep is not rlly needed) oNycamp and others (1998) awoke sleepers in REM for 15 minutes. Result: no sleepiness or REM rebound the next day oREM-blocking drugs cause periods of wakefulness

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* Many REM dreams are emotional, illogical, and prone to sudden shifts in plot * Non-REM dreams are shorter, more thought-like, repetitive, concern daily stresses * Dreams are usually associated with negative emotions and events --- Dreaming is our other state of consciousness (our internal) It is hard to study – experiments are subjective Rem dreams are different (lucid / more emotional ) than non rem sleep (story-like / they make sense / not emotional or exciting so you don’t rlly remember it) 75% of dreams are negative – sex dreams arw also low (9%)

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•80% of awakenings from REM yield reports of story-like dreams Common beliefs: * External stimuli may be incorporated into dreams * Dreams run on real time * Everyone dreams * Penile erections are not a result of erotic dreams * Sleepwalking and talking are less likely to occur while dreaming

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* Even people who claim NEVER to dream will describe dreams if awoken during REM * Prone to forgetting * High CBF in visual association areas - low in V1 and frontal areas * Dreams are high in visual content but poorly organized in time and rarely make sense -- During rem sleep – the whole frontal lobe is inactive -\> frontal lobe is not available to make any sense of any them -\>

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* Knowing you are dreaming while you’re asleep * Most of us have experienced one lucid dream * Usually very colourful and associated with anxiety * Opens the door to controlling our dreams! --- a skill you can apparantly develop

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•Biological clock (24 hour cycle)

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oLight = **zeitgeber** (timegiver) that entrains 24.18 hour clock to 24 hour cycle oEven a brief burst of light will reset our circadian rhythms oIf given soon after dusk then our clock is set back a few hours oIf given at after dawn, then our clock it set forward a few hours oWe use technology to be able to go to bed later and wake up later --- This is what keeos up awake – signals that keep our circadian rhythm alive Eating / physical activity / Light

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•Remove zeitgebers – still see circadian sleep-wake cycles? oFree-running periods vary, but are usually constant within a subject oMost are longer than 24 hours ~ 25 •What happens on days when you don’t need to get up?

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* Both will desynchronize circadian rhythms * Physical activity can be a zeitgeber * Solution is to get internal clock synchronized with external environment as quickly as possible

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* If you lesion this hypothalamic nucleus you disrupt circadian rhythms - will sleep in bouts during the day * Same amount of sleep, but won’t be synchronized * Some direct connections from visual pathways - retinohypothalamic pathway -- It gets information from our eyes -\> visual info from certaoins cells in the retina Tehse cells are timekeepers (active for 12 hrs not active for 12 hrs) If we take it away, we’ll still sleep but not for 24 hrs (no rhythm in ur sleep cycle) How does it do that?? -\> Melanopsin

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oPhotochemical in ganglion cells that transmit information from the retina to the rest of the brain oInvolved in papillary response as well -- It’s the change in light overtime activates this cell

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Pineal gland – essentially releases melatonin (our sleepy hormone) * Distributed to our body when we’re supposed to be sleepy / melatonin will be sleepy * It helps our circadian rhythm stay in circadian rhythm

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* Synthesized from serotonin in the pineal gland * Melatonin levels follow circadian rhythms controlled by the SCN * Pineal gland triggers seasonal reproductive changes in fish, birds, reptiles, and amphibians – human function is unclear * Melatonin is not a sleep aid, but may be used to shift circadian rhythms -- Keeps rhythm intact If your circadian rhytm is fine then you shouldn’t rlly take it

Answer 158

Two areas of the hypothalamus: - Economo found that the **posterior hypothalamus** and the **anterior hypothalamus** were related to excessive sleep or inability to sleep, respectively Findings were in patients that had encephalitis lethargica -- Hypothalamus -\> for motivation behaviors / sleeping behavior / 4fs The anterior hypo is most important for sleeping (if you damage it you will be asleep forever) Post is good for wakefulness (if u damage it ppl will be awake forever?)

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* Similarities between REM and wakefulness suggest that the same brain area might be involved in both * REM sleep is controlled by nuclei in the caudal reticular formation, each controlling a different aspect of REM

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* Affects 25% of population at some time * Must be defined in relation to a person's sleep needs * Paradoxically insomnia often caused by sleep medications because of tolerance - withdrawal cycle called **drug dependency insomnia** * People who report insomnia normally fall asleep within 30 minutes and get 6 hrs of sleep in a night

Answer 161

1. Don’t do anything stressful and relax before bedtime 2. Sleep and wake-up at regular times 3. Sleep in a cool room 4. Avoid caffeine, taking naps longer than 20 mins, or watching t.v. or surfing the web before bed 5. Sleep only when tired 6. Get out of bed if you can’t sleep and go back when you’re tired

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* Stop breathing (briefly) * Carbon dioxide in the blood stimulates chemoreceptors that causes the person to wake up gasping for air * Occurs in most people, especially those who snore * Obstruction of airway that can be surgically corrected

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* REM phenomena sneaking into waking hours * **Sleep attack** - overwhelming urge to sleep mostly during monotonous boring tasks. * Sleep generally lasts 2-5 minutes * Wake up feeling refreshed * Narcoleptic patients generally skip slow wave sleep and go directly to REM from waking

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* Inability to move just before the onset of sleep or when waking in the morning * Can snap out of it if poked or called by name * REM can also occur, such that the person dreams while lying awake - **hypnagogic hallucinations**

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* Opposite of cataplexy (paralysis) * Failure to exhibit paralysis during REM sleep * People act out their dreams * Could be a neurodegenerative disorder – usually associated with Parkinson’s Disease and MS * Could also be caused by brain damage to neural circuits in brainstem

Answer 166

* **Night terrors** * Most intense acceleration of heart rate in all of human experience - more rapid than 100 meter Olympic sprinters * STAGE 4 not REM * Crushed, suffocated, screaming, trembling – but do not remember * Usually harmless

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