hormones and cognition Flashcards
flashbulb memort
vivid memories of important, stressful events
not a separate memory function, but a class of memories that are:
a) more FREQUENTLY REHEARSED
b) more STRONGLY ENCODED
positive, yet stressful, events like weddings, births, lottery winnings are also remembered with great clarity
type of memory that operates without a NS
vaccines
human immune system can recognize something it has seen before and enact a response
all memory systems shared which abilities?
abilities to…
- enter info into storage (acquisition and consolidation)
- retain info
- retrieve info from storage
learning requires what to happen to info?
- input
- storage
- retrieval
why are effects of hormones on learning/memory based on task performance/observed behaviour?
because hard to measure learning directly
can only measure behaviour directly and quantitatively
BUT there are other ways by which hormones affect performance
hormones and memory: what steps can hormones affect?
all three of the INPUT, STORAGE and RETRIEVAL stages
psychological components of learning/memory
- motivation
- attention
- arousal
they all interact and affect one another
psychological components of memory can’t be directly measured, so…
only performance on tests designed to assess them can be measured
hormones and psychological components of memory
hormones = involved in arousal, motivation and attention
(and sensation, perception, emotion…)
hormones can affect the ANXIETY LEVEL independently from arousal during acquisition or memory testing
what can hormones affect independently from arousal?
anxiety level during acquisition or memory testing
one of the few laws of psychology
inverted U-shaped function of arousal
optimal performance on a learning task occurs at MODERATE AROUSAL LEVELS
if arousal is TOO LOW or TOO HIGH, learning is adversely affected
learning/performance: because hormones are involved in arousal…
they can have affects on learning/performance
learning
process of ADAPTIVE CHANGE IN BEHAVIOUR in response to EXPERIENCE
memory
encoding, storage and retrieval (or forgetting) of information about past experience
necessary for learning
hormones can affect any one or all of these stages of learning/memory
associative learning
learning about relationships through repeated experience
aka conditioning
sensitization
type of non-associative learning
stimulus that originally provoked little/no response begins to evoke a STRONGER response
after several presentations or a single intense presentation
habituation
type of associative learning
learning NOT TO RESPOND after repeated exposure to a stimulus
decrease in response to stimulus
results from reduction in amount of neurotransmitters released into the synapses
non associative learning
learning that doesn’t require pairing or stimuli association
altered response upon only one presentation
ie. sensitization
classical conditioning
response that was originally elicited by one stimulus can now be elicited by another stimulus that originally had no effect
learning represents the formation of an ASSOCIATION (pairing) between the two stimuli
Pavlovian conditioning
classical conditioning
operant learning
when animal performs an action in course of APPETITIVE or SEARCHING behaviour
frequently by accident
which is REINFORCED/REWARDED
often this single incident doesn’t lead to direct association of the action (operant) with its result (reinforcement)
but if act is performed several times, by CHOICE, and is reinforced EACH TIME…
association gradually builds
skinner box
used to measure instrumental learning/operant conditioning tasks
facilitates assessment of the ability of an animal to form an association between the BEHAVIOUR and its OUTCOME
active avoidance
form of associative learning
situation where animal must DO SOMETHING to AVOID a noxious situation
ie. mouse has to move to one side of Skinner box to avoid a shock
passive avoidance
form of associative learning
individual must SUPPRESS SOME BEHAVIOUR to that would otherwise be exhibited
ie. mice like the dark. mouse is placed in bright part of box, next to dark area. when it goes to dark part, it gets a foot shock. must go back to bright area to escape the sock
passive avoidance mouse skinner box: measure of strength of its memory
length of time the mouse remains in the lighted compartment
short term memory persists how long?
seconds to minutes
best way to move items from short to LTM
rehearsal
long term memory lasts how long?
days, weeks, years
no upper limit in capacity or retention
LTM splits into…
explicit (declarative) and implicit (non-declarative)
explicit splits into: semantic and episodic
implicit splits into: priming, conditioning, skill learning
working memory
similar to declarative and STM because it typically involves STM for info that changes on a regular basis
ie. remembering a phone number before you find paper to write it down on
reference memory
refers to associations/discriminations requiring REPETITIOUS LEARNING
ie. learning the rules
ie. putting keys in the same spot every time you get home
spatial memory
subcategory of memory that encodes info about the ENVIRONMENT and its ORIENTATION
3 main hormones that affect learning and memory
epinephrine
insulin
glucocorticoids
why don’t we know exactly how epinephrine works in the brain to store memory?
because it’s a polar molecule, so it doesn’t cross the blood brain barrier
epinephrine is released when…
learning occurs
generally enhances memory
u shaped function and epinephrine
u shaped function applies to epinephrine levels too
low and high blood levels of epinephrine impair memory
MODERATE levels ENHANCE memory
Yerkes-Dodson curve
u-shaped arousal curve
memory enhancing effects of norepinephrine depend on…
- dose
- timing
ie. animals perform better in avoidance situations after receiving a MODERATE rather than a mild foot shock
epinephrine potentiates…
the effects of the noxious stimuli used to train animals in active avoidance tasks
this is supported by the fact that epinephrine is released in response to stressful events
optimal epinephrine level for avoidance memory enhancement in rats
1500 pg/ml (in blood)
this level is observed in rats that show optimal performance in avoidance tasks
if 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 sum together…
and the animal exhibits OPTIMAL LEARNING
when is the best time to administer epinephrine?
immediately after training
if treatment comes BEFORE training or after SUBSTANTIAL TIME PERIOD has elapsed since training, it ISN’T EFFECTIVE in enhancing memory
temporal constraints on effectiveness of norepinephrine are consistent with…
hypothesis that epinephrine influences memory by potentiating the effects of noxious events
maybe because this time period is when memory is being consolidated
most effective timing of epinephrine administration in the rat avoidance task
injections are most effective in enhancing memory if given 1 minute after training
how does epinephrine enhance memory? background
doesn’t cross brain barrier - polar molecule
produced by very few neurons in brain as NT
and memory for passive/active avoidance tasks definitely resides in the brain
how can epinephrine secreted by adrenal glands affect learning and memory processes if it can’t get to neurons in the brain?
2 HYPOTHESES
how does epinephrine enhance memory? 2 hypotheses
- epinephrine activates PERIPHERAL RECEPTORS that directly influence brain function
- epinephrine affects memory via effets on BLOOD GLUCOSE LEVELS
hypothesis 1: epinephrine works via peripheral receptors
epinephrine modulates memory by activating peripheral receptors that communicate with the CNS
initiated by activation of peripheral BETA-ADRENOCEPTORS located on VAGAL AFFERENTS that project to nucleus of the solitary tract (NTS) in the brain stem
noradrenergic projections originating in NTS INNERVATE FOREBRAIN structures involved in LEARNING and MEMORY, including the amygdala
amygdala, epinephrine and memory
peripheral receptor hypothesis
epinephrine > beta adrenoreceptors > NTS > noradrenergic projections to AMYGDALA (and other forebrain structures)
amygdala historically considered to be involved in emotions
but also involved in LEARNING and MEMORY
how is amygdala involved in learning and memory?
directly and indirectly
via its close association with the HIPPOCAMPUS
electrical stimulation of amygdala can…
increase memory retention
vagus nerve
main nerves of parasympathetic NS
controls specific body functions like heart rate
what part of amygdala is especially involved in epinephrine action and memory?
basal lateral amygdala
basal lateral amygdala modulates…
memory of EMOTIONAL experience
by modulating MEMORY CONSOLIDATION via efferents to other brain regions
like caudate nucleus, nucleus accumbens, cortex
what prevents the memory-enhancing effects of epinephrine
blocking any part of the pathway
from beta-noradrenergic receptors on vagus nerve, to the neurons in the nucleus of the solitary tract (NTS) which project to basal lateral amygdala
peripheral receptor epinephrine hypothesis: story reading experiment SETUP
- read an EMOTIONALLY CHARGED or NEUTRAL story
- treated with PROPRANOLOL (beta-noradregernic antagonist)
peripheral receptor epinephrine hypothesis: story reading experiment RESULTS
those who read emotional story and were treated with propranolol…
had SIGNIFICANTLY IMPAIRED MEMORY
but memory WASN’T IMPAIRED for the neutral stories
peripheral receptor epinephrine hypothesis: story reading experiment TAKEAWAY
beta blockers affect emotional memories
but not non-emotional ones
peripheral receptor epinephrine hypothesis: story reading experiment RESEARCHERS RULED OUT…
researchers ruled out possibility that drug had NON-SPECIFIC EFFECTS on attention or motivation
support hypothesis that highly charged emotional memories REQUIRE ACTIVATION OF BETA-ANDRENERGIC RECEPTORS
the story reading experiment provides support for…
hypothesis that highly charged emotional memories require activation of beta-andrenergic receptors
because only memories of the emotional stories were reduced by the propanol
peripheral receptor epinephrine hypothesis: story reading experiment - alpha-amylase
alpha amylase (biomarker for adrenergic activity) was associated with emotional images but not to neutral images
alpha amylase
biomarker for adrenergic activity
PTSD
enhanced memories associated with arousing experiences = adaptive for avoiding future dangers
but when memories of fearful situations are intrusive, distressing and unwanted, can lead to PTSD
epinephrine and PTSD
variation among people in their FEAR-LEARNING and MEMORY MECHANISMS
as well as their RESPONSIVENESS TO EPINEPHRINE and NOREPINEPHRINE
can contribute to individual variation in PTSD SUSCEPTIBILITY
what can contribute to PTSD susceptibility?
- individual variation in FEAR LEARNING and MEMORY MECHANISMS
- individual variation in RESPONSIVENESS to EPINEPHRINE and NOREPINEPHRINE
hypothesis 2: epinephrine affects memory via its effect on BLOOD GLUCOSE LEVELS
epinephrine elevates blood glucose concentrations
this increases the amount of glucose that enters neurons in the brain
glucose enhances memory for AVOIDANCE LEARNING
as with epinephrine, effects of glucose are TIME-DEPENDENT
are glucose and peripheral receptor hypotheses of epinephrine and memory incompatible?
no
epinephrine elevates blood glucose concentrations, which increases the amount of glucose that enters neurons in the brain
glucose enhances memory for…
avoidance learning
time-dependent
injections of glucose delayed by an hour…
have no effects on retention and performance
but otherwise glucose enhances memory for avoidance learning
u shaped curve and glucose
u shaped curve also applies to glucose
there’s an optimal level (moderate) at which glucose enhances memory/performance
additional evidence for epinephrine blood glucose hypothesis
based on NEGATIVE FINDINGS
epinephrine blood glucose hypothesis: negative findings
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 MEM ENHANCEMENT PRODUCED BY GLUCOSE TREATMENT
epinephrine blood glucose hypothesis: negative results are consistent with notion…
reminder: mem enhancing effects are blocked by adrenergic antagonists, but not when mem enhancement is produced by glucose treatment
consistent with notion that GLUCOSE RELEASE is a memory modulating step that occurs SUBSEQUENT to release of norepinephrine
effects of glucose are DOWNSTREAM from peripheral epinephrine receptors, so they remain intact
most effective enhancers of mem and learning have what in common?
they all ELEVATE BLOOD GLUCOSE LEVELS
how does glucose enhance memory?
brain needs constant glucose supply in order to function
elevated blood glucose levels permit MORE GLUCOSE TO ENTER NEURONS
this in turn stimulates an increase in ACETYLCHOLINE RELEASE (excitatory NT)
increased acetylcholine levels = cognitive enhancement
glucose increases memory pathway
epinephrine > elevated glucose (brain needs constant glucose) > acetylcholine release (excitatory)
acetylcholine enhances cognitive function
glucose and memory: Alzheimer’s and AIDS
severe memory deficits observed in Alzheimer’s patients and AIDS correlate with MARKED REDUCTION in neurons that secrete ACETYLCHOLINE
glucose and epinephrine memory hypothesis: lemonade experiment SETUP
elderly people drank glass of LEMONADE
either prepared with SACCHARINE or GLUCOSE
glucose and epinephrine memory hypothesis: lemonade experiment RESULTS
elders who drank the glucose lemonade showed IMPROVED MEMORY FUNCTION relative to those who drank the saccharine lemonade
this WASN’T REPLICATED in YOUNGER PARTICIPANTS
glucose and epinephrine memory hypothesis: lemonade experiment - why were results only present in elders?
elderly people often have PROBLEMS REGULATING their BLOOD SUGAR LEVELS
normal decline in memory function during aging may reflect a diminishing ability to regulate blood glucose levels
glucose and epinephrine memory hypothesis: lemonade experiment - normal decline in memory function may reflect…
a DIMINISHING ABILITY to regulate BLOOD GLUCOSE levels
if unrelated blood glucose levels interfere with learning, then…
diabetics should display LEARNING DIFFICULTIES
and they do
although relationship between glucose regulation and cognitive impairment is well established, the association with insulin-dependent diabetes is not
cognitive effects of diabetes (in relation to glucose)
- most pronounced in older people, but also observed in young adult diabetics
- VERBAL MEMORY is most affected
- in Type 1 (insulin-dependent), cognitive impairments are linked with CHRONIC HYPERGLYCEMIA and recurrence of HYPOGLYCEMIA
- in Type 2 (non-insulin-dependent), onset of cognitive impairments could reflect DISRUPTIONS OF GLUCOSE METABOLISM or related problems (hyperglycemia, insulin concentration changes, hypertension, lipid level changes)
both types of diabetes negatively affect…
verbal reasoning
numerical reasoning
attention
concentration
verbal memory
visual memory
verbal fluency
diabetes may increase risk of…
dementia
impaired insulin signalling proposed as important in development of Alzheimer’s
type 3 diabetes
Alzheimer’s
impaired insulin signalling proposed as important in development of Alzheimer’s
why is Alzheimer’s called type 3 diabetes?
because its development has been linked to glucose signalling
because of glucose’s involvement in acetylcholine release and therefore cognitive abilities
since Alzheimer’s is defined by cognitive decline
where in the brain are insulin receptors most concentrated?
hippocampus
cortex
despite insulin not being needed for neuronal glucose uptake…
activation of brain insulin receptors are CORRELATED WITH ASSOCIATIVE LEARNING
abnormal insulin levels and reduced numbers of brain insulin receptors are common in Alzheimer’s patients with severe memory impairments
glucose use/metabolism in Alzheimer’s patients…
is reduced
regional glucose metabolism is observed in specific brain regions associated with…
memory in Alzheimer’s patients
EARLY DECREASES in cortical GLUCOSE utilization correspond to the same regions that later demonstrate the GREATEST DENSITY or senile PLAQUES and TANGLES
when considering the data on glucose and memory and Alzheimer’s together…
- glucose can enhance learning and memory
- impaired glucose metabolism can result in memory problems associated with Alzheimer’s and other forms of dementia
glucocorticoids and memory
memory can be enhanced by stressful events
acute stress appears to promote lasting memories, as does treatment with glucocorticoids
but chronic stress has opposite effects
memory and glucocorticoid treatment
treatment with glucocorticoids can promote lasting memories
glucocorticoid treatment prior to LEARNING WORDS/PICTURES improves recall on subsequent memory tests
but CHRONIC STRESS has opposite effects
brief versus chronic glucocorticoid exposure - learning/memory effects
BRIEF exposure to glucocorticoids (corticosterone or cortisol) ENHANCES learning/memory
CHRONIC exposure to glucocorticoids functions as an AMNESIAC
(back to the u-shaped curve idea)
morris water maze
rats must swim to find a submerged platform
finding the platform requires RELATIONAL LEARNING, because there are CUES to guide navigation
with time, rats learn to swim directly to the platform
morris water maze: glucocorticoids and learning/memory SETUP
three conditions
group 1: test 2 mins after electric shock
group 2: test 30 mins after electric shock
group 3: test 4 hours after electric shock
morris water maze: glucocorticoids and learning/memory RESULTS
because electric shocks resulted in ELEVATED CIRCULATING GLUCOCORTICOIDS about 30 mins later…
they caused stress and impaired memory performance
results suggest that elevated glucocorticoid concentrations at time of memory assessment impair performance
morris water maze: glucocorticoids and learning/memory TAKEAWAY
worst results came in group 2 (testing 30 mins after shock)
suggests that glucocorticoid release at time of memory assessment IMPAIRS performance
morris water maze: glucocorticoids and learning/memory - what improved performance?
treatment with a GLUCOCORTICOID RECEPTOR ANTAGONIST
directly into the dorsal hippocampus
chronically stressed animals and errors
chronic stress in animals causes them to commit MORE ERRORS
rats with highest corticosterone concentrations commit most errors Morris water maze
long-term corticosterone treatment and spatial learning
in rats, long-term corticosterone treatment IMPAIRS spatial learning in rats in variety of testing situations
glucocorticoids: improvements in learning and memory
sometimes, ACUTE stress ENHANCES performance on learning/memory tasks
improvements: glucocorticoids appear involved in both…
- hippocampus-dependent learning and memory
- hippocampus-independent learning and memory
single injections of natural or synthetic glucocorticoids…
mimic acute stress
tend to facilitate memory consolidation
natural or synthetic glucocorticoid example
dexamethasone
when are GRs activated by corticosterone?
typically only when CONCENTRATIONS ARE ELEVATED
like during ACUTE stressful EVENTS or during the CIRCADIAN PEAK of glucose secretion
evidence for idea that GRs are only activated by corticosterone when concentrations are elevated
- blocking specifically GRs causes IMPAIRED PERFORMANCE on spatial memory tasks in rats
- 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
- mice lacking GENE for GRs have substantial MEMORY DEFICITS
blocking GRs completely leads to…
memory impairments
ie. blocking intentionally, or in animals without the GR gene
glucocorticoids and memory enhancement: amygdala
memory-enhancing effects of glucocorticoids involve the AMYGDALA
amygdala modulates memory CONSOLIDATION process that occurs elsewhere in brain
basolateral amygdala integrates hormonal info that signals the hippocampus and other brain regions involved in memory consolidation
specific LESIONS of basolateral amygdala BLOCK memory-facilitating effects of glucocorticoids
infusions of GR-blocking DRUGS directly into basolateral amygdala impair memory consolidation
basolateral amygdala
INTEGRATES HORMONAL info that signals HIPPOCAMPUS and other brain areas involved in MEMORY CONSOLIDATION
lesions in basolateral amygdala
block the memory-facilitating effects of glucocorticoids
infusions of GR-blocking drugs directly into basolateral amygdala
impair memory consolidation
what does corticosterone do to the hippocampus?
restructures it
also affects other parts of the hippocampal circuit
ie. reductions in neuro-plasticity, spine density
hippocampus contains highest density of what in the brain? and why?
highest density of GRs
helps it mediate the regulation of the HPA axis
chronic stress hippocampus effects
chronic stress (thus high corticosterone)…
decreases number of PYRAMIDAL CELLS in hippocampus
low corticosterone hippocampus effects
somewhat paradoxical
cause DEGENERATION in dentate gyrus of hippocampus
(u-shaped curve)
Cushing syndorome
when adrenal glands produce EXCESSIVE CORTISOL
causes REDUCED HIPPOCAMPAL volume
2 examples of conditions resulting from altered glucocorticoid concentrations
- Cushing syndrome
- Addison disease
Addison disease
when adrenal glands produce INSUFFICIENT CORTISOL
causes necrosis of the GRANULE CELLS in the HIPPOCAMPUS
Addison and Cushing disease once more exemplify…
the u-shaped curve
Cushing = excessive cortisol = bad for hippocampus
Addison = not enough cortisol = bad for hippocampus
overview and potential future directions in behavioural endocrinology
- research in behavioural endocrinology informs EVOLUTIONARY THEORIES surrounding ultimate (“why”) questions by providing the proximate (“how”) explanations
- need for more HORMONAL ASSAY research, LONGITUDINAL designs, and experimental designs with EXOGENOUS HORMONE ADMINISTRATION
- more CROSS-CULTURAL research could illustrate important HORMONE INTERACTIONS with ENVIRONMENT, or REPLICATE key findings
- exploring complex REGULATORY NETWORKS that connect NEUROENDOCRINE SYSTEMS and their connection with OTHER physiological systems (immune and metabolic systems)
- behavioural endocrinology research typically focuses on a SINGLE HORMONE’S influence on a given trait, but physiological systems are INTERCONNECTED
