Lecture 11: Hormones and Cognition

Question 1

COMPONENTS OF LEARNING AND MEMORY

Answer 1

• Many of us maintain vivid memories of frightening events.
• In humans, the phenomenon of vivid memories of important, stressful events has been termed flashbulb memory.
• Flashbulb memory is probably not a separate category of memory function; rather, it probably represents a class of memories that are more frequently rehearsed or more strongly encoded. –> each generation tends to have its own unique flashbulb memory
• Positive, yet stressful, events such as weddings, births of
  children, or winning lotteries are also remembered with great
  clarity.
• Memory is not a unitary process; there are several types of memory systems, and some do not even require a nervous system.
• Males are better at visuospatial learning due to their higher levels of testosterone.

Question 2

!COMPONENTS OF LEARNING AND MEMORY

Answer 2

• All memory systems share the ability to:
  1. Enter information into storage (acquisition and consolidation)
  2. Retain information
  3. Retrieve information from storage
  These three components of memory must operate, or learning will not occur.

Hormones can affect any of these components of memory, or they can affect learning directly and thus memory indirectly.

However, it is rare to measure learning directly; only the results of learning can be measured and quantified. Consequently, statements about the effects of hormones on learning and memory are typically based on their effects on performance of a task, or observed behavior, but there are other ways by which hormones can affect performance on a learning task.
- hard to quantify because ….

Question 3

Psychological components of learning and memory

Answer 3

Psychological components of learning and memory:
* Motivation
* Attention
* Arousal.

These hypothetical constructs cannot be measured directly;
only performance on a test designed to assess one of these
constructs can be measured.

Learning, motivation, arousal, and attention interact and
affect one another.

Hormones are involved in arousal, motivation, and probably
also sensation, perception, attention, and emotion.
Additionally, hormones can affect the level of anxiety
independently from arousal during acquisition or memory
testing.

• Level of arousal low or very high
• U-shape is very importnant in psyc
• Hard to come up with laws in psyc but one common law is associated with the U-shape for perfromance on most test.

Question 4

Definition of Learning

Answer 4

Learning can be defined as a process that expresses itself as an adaptive change in behavior in response to experience. The stages of learning include acquisition, consolidation, retrieval, and extinction.
- through experience you learn something

Question 5

Definition of Memory

Answer 5

Memory—the encoding, storage, and retrieval (or forgetting) of information about past experience—is necessary if learning is to take place. Hormones can affect any one or all of these stages of learning and memory.

Question 6

Definition of No Associative Learning

Answer 6

Learning about relationships is called associative learning (frequently called conditioning)

Question 7

Definition of sensitization

Answer 7

Is one type of nonassociative learning in which a stimulus that originally provoked little or no response begins to evoke stronger responses after several presentations, or a single intense presentation provokes stronger responses to other stimuli.
- organism becomes more sensitive to the stimulus

Question 8

Definition of Habituation

Answer 8

Involves learning not to respond after repeated exposure to a stimulus. So it’s a decrease in response to a stimulus after repeated exposures. Habituation results from a reduction in the amount of neurotransmitter released into the synapses.
- learns not to react to stimulus

Question 9

Definition of classical conditioning

Answer 9

Classical conditioning: A response that was originally elicited by one stimulus can now be elicited by another stimulus that originally had no effect; in other words, learning represents the formation of an association (or pairing) between the two stimuli (Pavlovian conditioning)

Question 10

Definition of operant learning

Answer 10

Operant learning: Occurs when an animal performs an action in the course of appetitive or searching behavior, frequently by accident, which is reinforced or rewarded. Often this single incident does not lead to a direct association of the action (the operant) with its result (reinforcement - which will make the behaviour more likely), but if the act is performed several times, by choice, and is reinforced each time, the association gradually builds
- behaviour will eventually go away if reinforcement stops
- Casinos are an example of them using this.
- Relationships also - significant others reinforcing and then not reinforcing - intermittent reinforcement

• A Skinner box is used to measure instrumental learning (aka operant conditioning). It facilitates assessment of the ability of an animal to form an association between its behavior and the outcome of that behavior.

Question 11

Other forms of Associative Learning

Answer 11

• **Active avoidance: **Refers to a situation in which an animal must do something, that is, act, to avoid a noxious situation.
• Passive avoidance: A type of learning in which an individual must suppress some behavior that would otherwise be exhibited.

jump to illuminated part of box - and wont go back because they know that the chance of getting electrocuted in dark

Question 12

Short term memory

Answer 12

Short-term memory persists for seconds to minutes. Rehearsing is the best way to move items from short-term into long-term memory (mnenomic)

Semantic: learn a fact
Episodic: memory of experiencing something

Question 13

Long term memory

Answer 13

Long-term memory lasts for days, weeks, or years. Our long-term memory appears to have no upper limit in capacity or retention
DIVIDED IN:
- declarative: episodic and semantic
- Procedural/implicit memories (conditiioning, skill learning and priming)

Question 14

Memory: more definitions

Answer 14

Another way to categorize memory is by dividing it into working memory and reference memory.
* Working memory is similar to declarative and short-term memory in that it typically involves short-term memory for information that changes on a regular basis (effortful control/remembering of the memory).
* Reference memory, which generally refers to associations or discriminations requiring repetitious learning, as in learning the rules. ie: always putting the keys at the same spot
- could be a type of procedural memory
* Spatial memory Subcategory of memory that encodes information about the environment and its orientation. ie: knowing where in the field your keeper is

Question 15

THE EFFECTS OF HORMONES ON LEARNING AND MEMORY:
EPINEPHRINE

Answer 15

• We don’t know exactly how epinephrine works in the brain to store memories because it does not cross the blood brain barrier - it is a polar mechanism.
• Easily assessable, it was demonstrated that it is released
  when learning typically occurs.
• In general, epinephrine enhances memory.
• The U-shaped function of arousal, which is known as the Yerkes-Dodson curve, responses to different concentrations of epinephrine follow an inverted U-shaped curve; that is, low and high blood levels of epinephrine impair memory, whereas moderate epinephrine levels enhance memory.

epinephrine levels also resemble u-shape curve.

Question 16

Epinephrine, when is is released?

Answer 16

❑ Because epinephrine is released in response to stressful (traumatic/negative quality) events, a reasonable possibility is that epinephrine potentiates the effects of the noxious stimuli used to train animals in active avoidance tasks.
* The memory-enhancing effects of epinephrine are both dose- and time-dependent.
* For example, animals perform better in avoidance situations after receiving a moderate rather than a mild foot shock thus. A stronger shock is better because the milder shock does not elicit epinephrine release. Stronger stressor will ellicit the resposne but too strong = start to see u shape curve

Question 17

Optimal level of epinephrine for avoidance memory

Answer 17

• The optimal level of epinephrine for avoidance memory enhancement in rats is 1500 (pg/ml) in blood. This level is typically observed in rats that show optimal performance in avoidance tasks.
• If a mild foot shock produces blood epinephrine levels of 1000 pg/ml and this shock is paired with an injection that raises epinephrine levels another 500 pg/ml, then the exogenous and endogenous epinephrine sum together, and the animal exhibits optimal learning. Complementary use were able to have the rats reach optimal learning
• The best time to administer epinephrine is immediately after training; treatment either before training or after a substantial period of time has elapsed since training is not effective in enhancing memory These temporal constraints are consistent with the hypothesis that epinephrine influences memory by potentiating the effects of noxious events

Question 18

How does epinephrine enhance memory?

Answer 18

❖ Epinephrine is a polar molecule that does not easily cross the blood-brain barrier, although it is produced by a very few neurons in the brain as a neurotransmitter, and neuroscientists certainly agree that the memory for active and passive avoidance tasks resides in the brain.
❖ How can epinephrine secreted by the adrenal glands affect learning and memory processes if it cannot get to the neurons in the brain? The 2 hypothesis:
- Epinephrine activates peripheral receptors that directly influence brain function hypothesis
- Epinephrine affects memory via its effect on blood glucose levels hypothesis

Question 19

How does epinephrine enhance memory? Epinephrine activates peripheral receptors that directly influence brain function hypothesis

Answer 19

• Epinephrine modulates memory by activating peripheral receptors that communicate with the central nervous system.
• Many experiments indicate that epinephrine effects on memory consolidation are initiated by activation of peripheral βadrenoceptors located on vagal afferents that project to the nucleus of the solitary tract (NTS) in the brain stem.
• Noradrenergic projections originating in the NTS innervate forebrain structures involved in learning and memory, including the amygdala
• Although the amygdala has been considered for years to be involved in emotions, this of the limbic forebrain is also involved in learning and memory, both directly and indirectly via its close association with the hippocampus.
• Electrical stimulation of the amygdala can also increase memory retention

Question 20

How does epinephrine enhance memory?

Answer 20

Effects memory of emotional experiences blocking the pathway surgically or with drugs

Question 21

Epinephrine + human memory

Answer 21

• In humans, individuals that read either an emotionally charged story or a similar story that was judged by other people to be more emotionally neutral, and treated with propranolol, a potent βadrenergic antagonist, had significantly impaired memory of the emotionally arousing stories but did not affect memory of the neutral ones
• The researchers who conducted this study were able to rule out the possibility that the drug had nonspecific effects on attention or motivation. These results support the hypothesis that highly charged emotional memories require activation of β-adrenergic receptors.

Question 21

Epinephrine and PTSD

Answer 21

• Possession of enhanced memories associated with arousing experiences is inherently adaptive for avoiding danger in the future. When memories of fearful situations are intrusive, distressing, and unwanted, they can lead to disorders such as post-traumatic stress disorder (PTSD).
• The role of epinephrine and norepinephrine in the development and maintenance of PTSD are currently being investigated. It seems possible that variation among people in their fear-learning and memory mechanisms, as well as their responsiveness to epinephrine and norepinephrine, may contribute to individual variation in susceptibility to PTSD

Question 22

How does epinephrine enhance memory? Epinephrine affects memory via its effect on blood glucose levels hypothesis

Answer 22

❖ The glucose and peripheral receptor hypotheses of how epinephrine affects memory are not incompatible. Epinephrine elevates blood glucose concentrations, which increases the amount of glucose that enters neurons in the brain.
❖ In general, glucose enhances memory for avoidance learning.
❖ As with epinephrine, the effects of glucose are time-dependent; injections of glucose delayed by 1 hour after training have no effect on retention and performance.

These two pathways seem to be complimentary and not dependent.

Question 23

How does epinephrine enhance memory? Epinephrine affects memory via its effect on blood glucose levels hypothesis

Answer 23

• Additional evidence that epinephrine produces its effects on memory by raising blood glucose levels is based on negative findings.
• The memory-enhancing and memory-impairing effects of epinephrine treatment can be blocked by treating animals with adrenergic antagonists, but these blockers have no effect on memory enhancement produced by glucose treatment.
• These results are consistent with the notion that glucose release is a memory modulation step that occurs subsequent to the release of epinephrine. With the effects of glucose, which are “downstream” from the peripheral epinephrine receptors, remaining intact.
• The agents most effective in enhancing human cognitive
  performance (improving learning and memory) share a common feature: they all elevate blood glucose levels

Question 24

How does glucose enhance memory? Epinephrine affects memory via its effect on blood glucose levels hypothesis

Answer 24

❑ The brain requires a constant supply of glucose in order to function. ❑ Elevated blood glucose levels permit more glucose to enter neurons, which in turn stimulates an increase in the release of the neurotransmitter acetylcholine (excitatory) from neurons in the brain. ❑ Increases in acetylcholine levels in the brain synapses are characteristic of all known cognitive enhancers - acetylcholine increases cognition. ❑The severe memory deficits observed in patients with advanced Alzheimer’s disease or AIDS are correlated with a marked reduction in neurons that secrete acetylcholine.

Question 25

How does glucose enhance memory? Findings with human elders

Answer 25

Findings with human elders: * Elderly participants were asked to drink a glass of lemonade that had been prepared with either saccharine or glucose. Interestingly individuals who had received glucose (lemonade) showed improved memory function relative to those who drank lemonade prepared with saccharine. - glucose metabolism is altered in Alzeihmer's * **This was not replicate in young participants** One possible reason is that elderly people often have problems regulating their blood sugar levels. The normal decline in memory function during aging may thus reflect a diminishing ability to regulate blood levels of glucose.

Question 26

THE EFFECTS OF HORMONES ON LEARNING AND MEMORY: INSULIN

Answer 26

**INSULIN** If unregulated blood glucose levels interfere with learning, then diabetic animals and humans should display learning difficulties. This is something that we actually see. ❑ Although the relationship between glucose regulation and cognitive impairment is well established the association with insulin-dependent diabetes is not. - several cognitive deficits associated with diabetes.

Question 27

Diabetes effect on Cognition

Answer 27

❑ Both types of Diabetes negatively affect measures of verbal and numerical reasoning, attention, concentration, verbal and visual memory, and verbal fluency. ❑ Diabetes may also increase the risk of dementia ❑ Impaired insulin signaling has been proposed as important in the development of Alzheimer’s disease, what sometimes are referred as Type-3 diabetes.- not necessarily are diabetic... Not super clear what insulin does in the brain...some modulatory effects.

Answer 28

* purple regions = observe reduced utilization of glucose. * Brain alterations also regions that show reduction in glucose utilization. * plaques are also regions associated with glucose level alteration * Type 3 diabetes = early marker for alzeihmers.

Question 29

THE EFFECTS OF HORMONES ON LEARNING AND MEMORY: Glucocorticoids

Answer 29

❑ Memory can be enhanced by stressful events (exposure to glucocorticoids). - something that makes you lose memories = amnesic - see u-inverted shape curve for cortisol as well. ❑ Acute stress appears to promote lasting memories, as does treatment with glucocorticoids. Treatment of people with glucocorticoids prior to learning words or pictures, for example, improves their recall on subsequent memory tests. ❑ Chronic stress, however, seems to have the opposite effect. ❑ Brief exposure to glucocorticoids (corticosterone or cortisol) enhances learning and memory, whereas chronic exposure to glucocorticoids appears to function as an amnestic

Question 30

GLUCOCORTICOIDS Impairments in learning and memory

Answer 30

* They dye the water * which group preformed worse if you think about cortisol release? cortisol is released in long term response so the animals in the 30 mins group showed impaired spatial memory in this task. * if the shock was too much, it would impair their ability due to too much release of cortisol.

Question 31

GLUCOCORTICOIDS Impairments in learning and memory on the long-term

Answer 31

❖ Chronically stress animals tend to commit more errors. Also, rats with the highest corticosterone concentrations displays the most errors in performance. ❖ Treatment with a glucocorticoid receptor antagonist infused directly into the dorsal hippocampus improved the performance of rats in the Morris water maze. ❖ Subsequent studies have shown that long-term corticosterone treatment impairs spatial learning in rats in a variety of testing situations

Question 32

GLUCOCORTICOIDS Improvements in learning and memory

Answer 32

❖ In some cases, acute stress enhances performance on learning and memory tasks. ❖ Glucocorticoids appear to be involved in facilitation of both hippocampus-dependent and hippocampus-independent learning and memory. ❖ Single injections of natural or synthetic (e.g., dexamethasone) glucocorticoids mimic acute stress and tend to facilitate memory consolidation ❖ Depending on the brain area and the level of corticol release, we can see impairments. Typically, GRs are activated by corticosterone only when concentrations are elevated, such as during acute stressful events or during the circadian peak of glucocorticoid secretion. Evidence of this comes from different species: 1 - Blocking specifically GRs, impaired performance on spatial memory tasks in rats 2 - The enhancing effects of either acute stress or corticosterone treatment on memory for a passive avoidance task could be blocked by blocking GRs in day-old chicks. 3 - Mice lacking the gene for GRs display substantial memory deficits. Keep in mind the u-shaped curve, sometimes blocking GR completely can lead to imparements but also too much cortisol can lead to impairement too.

Question 33

GLUCOCORTICOIDS Improvements in learning and memory

Answer 33

Amygdala is also involved: ❖ The memory-enhancing effects of glucocorticoids appear to involvethe amygdala, which modulates the memory consolidation process that probably occurs elsewhere in the brain. ❖ The basolateral amygdala appears to integrate hormonal information that signals the hippocampus and other brain regions involved in memory consolidation. ❖ Specific lesions of the basolateral amygdala block the memory facilitating effects of glucocorticoids, and infusions of GR-blocking drugs directly into this region impair memory consolidation. We have GR in amygdala and hippocampus. Depending on the levels of these we can have impairement or learning.

Question 34

GLUCOCORTICOIDS Hippocampus and glucocorticoids

Answer 34

❖ Corticosterone can cause restructuring of the hippocampus and parts of the so-called hippocampal circuit. - reduction in spine density and spines in the hippocampus ❖ The hippocampus contains the highest density of GRs in the brain and mediates the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. ❖ Chronic stress, thus high corticosterone exposure, decreases the number of pyramidal cells in the hippocampus, and somewhat paradoxically, very low corticosterone concentrations cause degeneration in the dentate gyrus of the hippocampus - Remember the U-shaped patterns that we mentioned several times today!

Question 35

Humans with altered glucocorticoid concentrations:

Answer 35

o Patients with **Cushing syndrome**, whose adrenal glands produce excessive cortisol, have reduced hippocampal volumes o Patients with **Addison disease**, whose adrenal glands produce insufficient cortisol, show necrosis of the granule cells in the hippocampus U-shaped patterns are also observed in both these cases.

Question 36

CLASS SUMMARY

Answer 36

* Several types of learning have been documented, including sensitization and habituation, as well as associative learning. There are also several types of memory, including short-term memory (working memory) (spatial and nonspatial); long-term memory. Hormones affect each type of learning and memory. * The hormones that are associated with adaptation to stress enhance learning and memory. * There are two hypotheses regarding how epinephrine affects memory: (1) epinephrine may affect memory via its effect on blood glucose levels (2) epinephrine may activate peripheral receptors that directly influence brain function. * Elevated blood glucose levels facilitate the movement of glucose into neurons. More glucose entering neurons stimulates the release of more acetylcholine into the neuronal synapses. * Although acute/short term glucocorticoids or stressors enhance learning and memory, chronically elevated glucocorticoids or chronic stress impair spatial learning and memory although interactions with sex steroids are possible.