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Biol 405: Comparative Endocrinology > Exam 4 > Flashcards

Exam 4 Flashcards

1
Q

Any perturbation to homeostasis requires an animal…….

A

to expend energy to restore steady state

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2
Q

Stress simple definition

A

any significant disturbance of homeostasis (environmental factors, physiological factors, psychosocial factors)

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3
Q

Homeostatic definition of stress

A

Sum of all nonspecific effects of factors that can act on the body to increase energy consumption significantly above a resting (basal) level

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4
Q

Limitations of homeostatic definition

A
  • Psychological stressors can elicit a full physiological stress response (and cause homeostatic imbalance)
  • Does not account for individual variation in the perception of stressors
  • The physiological response to stress can be caused by stressful and pleasurable events
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5
Q

Alternative definition of stress

A
  • individuals are aroused by aversive stimuli
  • Individual must perceive stressful event as aversive
  • Stress depends on an individual’s perception of their control over the aversive stimuli
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6
Q

Stressor

A
  • a stimulus that disrupts physiological homeostasis
  • threats against homeostasis
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7
Q

Stress response

A
  • physiological and behavioral responses that help reestablish homeostasis
  • norepinephrine and epinephrine increase cardiovascular tone, respiration rate, blood flow, glucose levels, alertness
  • Activated when perceived degree of control over situation is low (ex: preparing for an exam)

body’s attempt to reestablish homeostasis

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8
Q

Two endocrine systems involved in stress reponse

A
  • Fast response: norepinephrine from sympathetic nervous system and epinephrine from adrenal medulla
  • Slow(er) response: glucocorticoids from adrenal cortex
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9
Q

“Fight or flight response”

A

immediate, non-specific component of the stress response, autonomic and endocrine responses that prepare organism to fight/flee from a real/ perceived threat

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10
Q

How does stress of parachute jumping alter [blood hormone]?

A

first day of parachute jumping: Glucocorticoids, norepinephrine, and epinephrine increase; Testosterone suppressed
As jumpers gain confidence: all return to baseline

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11
Q

how does epinephrine and norepineprhine stress response if cant cross BBB?

A

release of epinephrine and norepinephrine from the adrenal medulla –> HPA release Glucocorticoids ,which bind to glucocorticoid brain receptors

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12
Q

What do CRH neurons in the PVN release?

A

PVN release CRH onto anterior pituitary gland → ACTH and β-endorphin released into the bloodstream

ACTH causes the adrenal cortex to release glucocorticoids

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13
Q

What do high levels of glucocorticoids feedback (negative feedback) to the brain do?

A

shut off the stress response, allowing a return to homeostasis

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14
Q

general adaptation syndrome and 3 stages

A

Process of coping with stressors
1. alarm reaction (2 days)-
stressor is detected, decreased resistance to stress, physiological systems can deteriorate (endocrine glands and immune cells atrophy)
2.resistance (2 weeks)-
coping with stressor, resistance to stress via increased adrenal function (glucocorticoids, epinephrine)
3. exhaustion (2 months)- Stress response stops, occurs if stress is prolonged or resistance fails, physiological and behavioral coping mechanisms fail

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15
Q

Stress response adaptive effects

A
  • Increased immediate availability of energy
  • Increased oxygen intake
  • Enhanced sensory function and memory
  • Decreased blood flow to organ systems not necessary for movement
  • Inhibition of energetically expensive processes not related to immediate survival (digestion, growth, immune function, reproduction)
  • Decreased pain perception
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16
Q

Nonspecific response

A

both predator and prey experience similar stress responses

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17
Q

Restraint stress

A
  • enhances immune response in intact and sham-operated rodents (does not enhance immune response in adrenalectomized rodents)
  • Adaptive improvement of immune function requires glucocorticoids

acute stress can improve immune function

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18
Q

Effect of stress on vasopressin

A

increased vasopressin –> increases blood volume and BP, makes delivery of energy to muscles more efficient, enhances memory consolidation and aggression

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19
Q

Effect of stress on urocortin

A

Increased urocortin--> amplifies stress signals by activating CRH neurons

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20
Q

Effect of stress on prolactin

A

Increased prolactin:
→ testes become less responsive to LH and produce less testosterone, → enhanced negative feedback to testosterone in hypothalamus and pituitary

temporarily inhibits reproduction by acting on multiple sites within the hypothalamic-pituitary-gonadal axis:

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21
Q

Effect of stress on glucagon

A

Increased glucagon –> inhibited insulin increase energy availability

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22
Q

Effect of stress on endorphins

A

Increased endorphins –> suppress GnRH and inhibit reproductive function

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23
Q

Explain why stress is said to be highly adaptive

A

improves the chances of survival by shifting from nonessential processes to those that promote immediate survival

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24
Q

why is stress only adaptive in the short term?

A

prolonged stress shifts the adaptive stress response to a pathological condition: chronic stress

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25
Q

What does it mean that humans are commonly chronically stressed?

A

our bodies remain engaged for emergency activation even though we may be physically inactive

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26
Q

Pathological effects of chronic stress

A

effects on cardiovascular, metabolic, reproductive, immune, behavioral, and psychological processes

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27
Q

Prolonged glucocorticoid secretion

A
  • Muscle loss, inhibits reproductive, digestion, & immune function
  • Delays cutaneous wound healing in both rodents and humans: caregivers for chronically ill spouses show increased cortisol levels and slower wound healing than controls
  • Reduces neurogenesis in the hippocampus, causes pruning of dendrites on neurons in the hippocampus and cortex
  • Increases inflammation in the brain that impairs memory
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28
Q

Explain the “Inverted U” relationship of stress on cognitive and mental performance

A
  • Acute stress: can improve brain function to optimize attention, behavior, and cognitive function; increases neurogenesis
  • Chronic stress: greatly decreases brain function, reduces learning and memory, impairs neurogenesis
  • Duration of stress (x); cognitive performance (y)
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29
Q

Effects on dominant and subordinate baboons

A
  • both have elevated glucocorticoids in response to stres
  • Dominant baboons: HPA axis quickly activates negative feedback and glucocorticoid levels return to baseline
  • Subordinate baboons: HPA axis negative feedback is poorly regulated and glucocorticoid levels stay elevated
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30
Q

Brains of stressed fetuses and infants are ………… from the brains of individuals that do not experience stressors early in development

A

organized differently

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31
Q

Brains of stressed fetuses and infants are differentially activated by ……..

A

glucocorticoids in adulthood

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32
Q

Effects on male offspring of chronically stressed pregnant rats

A

Altered testosterone levels right after birth → blocks the sexually dimorphic development of the POA → don’t have normal mating behavior in adulthood, even though normal testosterone

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33
Q

Effects on female offspring of chronically stressed pregnant rats

A

Normal estrous cycles, mating behavior, and maternal behavior

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34
Q

Effects on offspring of chronically stressed pregnant rats

A

Dysregulated HPA axis negative feedback (and have elevated glucocorticoid levels)

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35
Q

Effects on offspring if stressed mother is adrenalectomized

A

Offspring have normal levels of glucocorticoids and normal negative feedback

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36
Q

Effects of high levels of glucocorticoids on prenatally stressed primates (humans and monkeys) and infants in utero

A
  • reduced birth weights, developmental delays
  • impaired neuromotor development
  • attention deficits, impaired social behavior
  • increased anxiety
  • increased rats of cardiovascular and metabolic disorders
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37
Q

Elevated glucocorticoid levels during early pregnancy are associated with………

A

increased amygdala size and poor emotional development in girls (but not boys) prior to puberty

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38
Q

Evidence that early stressful experiences affect reactions to stress later in life

A

If a rat pup experiences mild stress, it is better able to cope with stress later in life

Mothers spend extra time licking pups that are stressed; Maternal tactile cues (licking, contact) stop glucocorticoid and ACTH release in pups from stress

Pups that received more maternal attention exhibit lower stress responses (glucocorticoid and ACTH release) as adults

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39
Q

What how does stress immunization effect affect pups later on in life?

A

allows pups to cope with stress better as adults, likely due to changes in responsiveness of HPA axis negative feedback (acute)

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40
Q

What does chronic separation of pups from mothers cause?

A

enduring inhibition of neurogenesis and hippocampal function as adults due to hypersensitivity to normal glucocorticoid concentrations

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41
Q

Epigenetics of high levels of pup licking

A

increases serotonin levels in hippocampus, which increases levels of NGF1-a –> demethylates glucocorticoid receptor gene and acetylates nearby histones —> easily bind to the glucocorticoid receptor gene → permanent increase in glucocorticoid gene expression in the hippocampus

When the pups become adults, their high levels of hippocampus glucocorticoid receptor levels enhances HPA axis negative feedback, leading to lower glucocorticoid levels

This leads to female pups adopting their mother’s high level of maternal care as adults

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42
Q

Infant rhesus monkeys separated from mothers immediately following birth provided with two surrogate mothers

A

Wire mother: wire frame with nipple, provided nutrition (milk)
Cloth mother: wire frame covered with soft material but did not provide nutrition

When stressed by an intruder, infant ran to cloth mother for comfort (can cling for contact comfort)
Contact with mother is a powerful “buffer” for the HPA axis against stressful situations in non-human primates

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43
Q

Glucocorticoid levels in human children in group day care versus those who stay home,

A

group day care kids have elevated glucocorticoid levels

associated with impaired self-control and attention

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44
Q

Glucocorticoid levels in:
>8-month-old children adopted from orphanages in war-torn countries 6+ years later

vs

children adopted < 8 months of age or children adopted from domestic orphanages

A

Higher glucocorticoid levels in children adopted from orphanages in war-torn countries

Greater likelihood of long-term behavioral problems, endocrine dysregulation, PTSD, brain dysfunction

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45
Q

Psychosocial dwarfism

A

disorders of stunted growth and development despite adequate nutrition, caused by neglect and abuse

Abnormal GH release, absence of response to GH treatment, but usually recover after placement in hospital or “good” home environment

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46
Q

Effects on pups after separation from the mother

A

-ODC and GH drop immediately in all tissues involved in the regulation of protein synthesis, tissue growth, development
-GH in the blood decreased: regulates ODC activity in the brain and body
-Glucocorticoids in the blood increased

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47
Q

Effects on pups shortly after reuniting pups and mother

A

ODC enzyme and GH concentrations return to normal, but only if the mother is “interactive” → anesthetized lactating mother does not restore ODC or growth hormone levels

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48
Q

Effects on pups after receiving GH injection

A

no effect

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49
Q

Effects of stroking isolated pups with a damp paintbrush

A

restores ODC and growth hormone levels

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50
Q

what happens when rats taken away from mother?

A

pups can’t be licked → stunted growth rate

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51
Q

what happens when mothers lick pups?

A

dropped Glucocorticoids → increased ODC

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52
Q

how do glucocorticoids affect growth hormone levels?

A

suppress GH levels

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53
Q

Sex differences in stress responses are ……., but not …….. by……..

evidence

A

activated but not organized by hormones

ovariectomy in adulthood eliminates the sex difference in the HPA axis, and estrogen therapy restores it

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54
Q

How does stress affect GnRH and LH secretion

A
  • POMC cleaved into endorphins more than ACTH –> opioids inhibit GnRH and LH secretion
  • High [glucocorticoids] directly inhibits GnRH and LH secretion, inhibit LH receptors in the testes
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55
Q

Heroin addicts effects on GnRH and LH secretion

A

have impaired GnRH and LH secretion, sexual motivation, and performance;

can all be reversed with opioid receptor antagonist

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56
Q

Evidence that more B-endorphin release is an effect of stress

A

Heroin addicts have impaired GnRH and LH secretion, sexual motivation, and performance

can all be reversed with opioid receptor antagonist

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57
Q

How do high [glucocorticoid] affect GnRH and LH secretion?

A

enzyme that breaks down glucocorticoids becomes overwhelmed, leading to an overstimulation (“exhaustion”) of the glucocorticoid receptors and
suppression of testosterone production

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58
Q

How does stress affect male fertility?

A

Low [testosterone] don’t support spermatogenesis: stressed animals become infertile

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59
Q

Dominant rat fertility

A

have more enzyme that breaks down glucocorticoids in the testes, which counteracts elevated glucocorticoid levels, allowing testosterone to remain high, leading to fertility even when stressed

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60
Q

How does stress affect prolactin release in males?

A

increases levels of prolactin release, which can inhibit male reproductive function by enhancing testosterone negative feedback

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61
Q

What autonomic nervous system has to be activated to initiate erection vs ejaculation?

A

Parasympathetic: to initiate erection
Sympathetic: to cause ejaculation

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62
Q

How does high sympathetic nervous activity during stress affect erection?

A

difficult to establish parasympathetic activity: erectile dysfunction

sympathetic nervous system input to the penis to be activated too quickly: premature ejaculation

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63
Q

In males, sexual behavior can proceed with …….

A

very low levels of testosterone (and sometimes without testosterone)

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64
Q

Effect of stress on cycles

A
  • Can disrupt estrous cycles in animals & menstrual cycles in human women
  • Women with disrupted menstrual cycles exhibit elevated glucocorticoid levels
65
Q

Elevated levels of glucocorticoids in females

A

(like males) directly suppress GnRH and LH secretion and inhibit LH receptors in ovaries

66
Q

How does stress affect pregnancy and lactation

Example

A

can interrupt pregnancy and lactation: glucocorticoid levels are inversely related to litter size, offspring weight, and body size in many species

Pregnant rabbits briefly exposed to a predator during gestation have high levels of glucocorticoids and greatly decreased number of viable litters

67
Q

How does rigorous diet or extrenous exercise affect fertility? Evidence?

A
  • have problems with fertility
  • LH pulses less frequent in long-distance runners, who have higher incidence of amenorrhea
  • Stress-induced reproductive inhibition occurs among females of all mammalian species and is entirely reversible upon relaxation of energy demands
68
Q

Effect of stress on adrenal cortex in males and females

A

adrenal cortex produces androgens in small amounts in addition to glucocorticoids

69
Q

Stress on adrenal glands

A

increase androgen secretion

in females can interrupt reproduction: interrupt HPA negative feedback, GnRH secretion, and LH secretion

70
Q

Chronic stress before mating in female rats

A

causes significant reproductive dysfunction: fewer successful copulations and pregnancies

71
Q

Stress on GnIH in females

A

Increased levels of GnIH in the hypothalamus

genetically silencing GnIH during chronic stress leads to normal fertility

72
Q

Individual animals that “ignore” stressors and breed normally:

A
  • Aged animals with minimal future prospects for reproductive success
  • Seasonal breeders that have a truncated breeding season because of challenging conditions at the end of each season
  • Biparental species where one member of the pair dies
  • Semelparous breeders that have a single breeding period followed by death
  • Individuals where window of breeding opportunities is short because of rapidly shifting social organization
73
Q

Mechanisms for ignoring stressors include adjustments to:

A
  • The central nervous system (no longer perceive the situation as stressful)
  • HPA axis to prevent elevated glucocorticoid levels
  • HPG axis (glucocorticoids somehow no longer impede HPG function)
  • HPG and HPA axis simultaneously
74
Q

What happens to population if rats put in large cages, provided with food and water, and allowed to breed? Why?

A
  • population rises dramatically, but suddenly crashes
  • Dead rats had enlarged adrenal glands and excess glucocorticoids
  • Not due to overcrowding: even if group-housed rats had 3x the amount of floor space they still exhibit stress response

Social interactions at higher population densities cause stress response

75
Q

social behavior: African wild dogs dispersal

A
  • live in packs of 8 adults but only have one breeding pair (“alpha pair”) per pack
  • Subordinate female disperse (leave their natal packs) and attempt to become alpha females elsewhere: must attack and dominate current alpha female
  • Dispersal causes social instability: dominant females must constantly attempt to defend their status against dispersed females
  • Dominant females have higher glucocorticoid levels than subordinate females
76
Q

Relationship between hormones and behavior is…..

and how?

A

bidirectional

Stress causes hormonal changes, which affect brain processes, which affect behavior, but the brain itself can elicit a full stress response and glucocorticoid release to affect physiology and behavior

77
Q

What are the psychological variables that can modulate stress physiology?

A
  1. control
  2. predictability
  3. outlets for frustration
  4. habituation
78
Q

Psychological factors in stress: control

A
  • Individuals suffer fewer stress-related pathologies if they can control the situation causing the stress
  • Rats that can control frequency of electric shock have lower levels of glucocorticoids than rats given random shocks
79
Q

How do rats respond to given daily restraint stress?
What is this an example of?

A

Eventually show the same stress response (number of fecal pellets produced) as control

unless the daily restraint stress is interrupted

Habituation

80
Q

Psychological factors in stress: predictability

A
  • Knowing a stressor is coming reduces the stress response
  • If warning signals are given to rats prior to shocks, those rats have lower glucocorticoid concentrations (and stress pathology like ulcers) than rats given random shocks
  • Intense but unexpected stressors can have enduring effects on the brain
81
Q

Study on people who were close to world trade center on 9/11

A

significant reductions in brain volume in amygdala, hippocampus, cortex when measured 3+ years later

82
Q

Psychological factors in stress: outlets for frustration

A
  • The ability to engage in “displacement behavior” reduces the stress response
  • Rats that are shocked but can chew on a piece of wood or attack another rat have lower levels of glucocorticoids
  • Even modest outlets can decrease stress response: children engaging in leg swinging activity in response to the stresses of school have lower heart rates due to increased parasympathetic nervous system activity (perception of control)

displacement behavior- out-of-context behavior

83
Q

Psychological factors in stress: habituation

A
  • Learning that a stimulus originally perceived as a stressor is not actually a stressor
  • Need to be presented with same stimulus repeatedly but without aversive context (harmless)
  • Squirrels normally avoid humans but eventually stop running away when they learn humans will feed them
  • Parachuters jumping out an airplane several times will eventually learn that they are safe and will not have a stress response
84
Q

memory vs learning

A

Memory: encoding, storage, and retrieval (or forgetting) of information about past experience
Learning: adaptive change in behavior that results from experience

85
Q

Ultimate level of causation on memory

A

marking of important (stressful) events into memory could enhance learning about adaptively significant aspects (i.e., dangers) of the world

86
Q

Only the……… learning can be measured and quantified

A

the results of learning

(based on performance on task or on observed behavior)

87
Q

…….. ……… ………. as a physiological marker of “importance” for memories

A

hormones released during stress or high arousal

88
Q

What 3 components of memory can hormones affect?

A
  1. encoding (acquisition)
  2. storage (retention- short/long term)
  3. retrieval (how they access stored info- Recall, recognition, relearning)
89
Q

can hormones affect memory indirectly?

A

Yes, they can affect learning directly and therefore memory indirectly

90
Q

Non-associative learning

A

change in strength of response to a stimulus after repeated exposure to a stimulus, generalized and simple learning that occurs in all animals

sensitization and habituation

91
Q

Sensitization definition and example

A
  • amplification of a response after repeated presentation (or single intense presentation) of a stimulus that originally provoked little/ no response
  • ex: after you experience a very loud noise, a slight noise that normally would have no reaction can elicit a startle response
92
Q

Habituation

A
  • decrease in response (learning not to respond) to a stimulus after repeated exposure, can occur in simple invertebrates, cells in a dish
  • Results from reduction in amount of neurotransmitter released
93
Q

How are fatigue and sensory adaptation not examples of habituation?

A

Not fatigue: loss of efficiency in performance on motor act after repetitions – you do not “forget” how to do chin ups
Not sensory adaptation: occurs at the level of the receptor, sensory receptors stop sending signals to brain (ignore sensation of wearing clothes) – with habituation the signals still arrive but the brain ignores them

94
Q

associative learning

A

an association between two stimuli is established or relationship between stimuli is learned, also called conditioning

classical conditoning, operant learning, active avoidance, passive avoidance

95
Q

Classical conditioning

A

response originally elicited by one stimulus can be conditioned to be elicited by another that originally had no effect

US: stimulus that evokes a response without prior experience (meat) no association needed
UR: innate reflex response to the unconditioned stimulus (salivate)
Neutral S/R: stimulus that normally does not evoke a response (bell)
Classical conditioning: repeatedly pair neutral stimulus with unconditioned stimulus
CS: neutral stimulus after classical conditioning (bell)
CR: response to the conditioned stimulus (salivate)

96
Q

What is operant learning

A
  • animal performs an action, typically by accident, which is reinforced or rewarded
  • Single incident does not lead to association between operant (the action) and the reward, but if action is reinforced several times, animal gradually forms an association
97
Q

Example of operant learning on rat

A

Give rat a small reward each time it presses a lever (by accident or while exploring), rat will begin to press lever to receive a reward

98
Q

Extinguishment definition

A

If reward removed, response is extinguished (goes away) but how long it takes to go away depends on how behaviors are learned

99
Q

Examples of operant conditioning on humans

A
  • EX: receive reinforcement (food or drink) every time you put money in a vending machine, if you put money in and receive nothing you will quickly stop
  • EX: conditioned to receive reinforcement (slot machine payout) after a random number of times you put money in the slot machine. If you put money in and receive nothing, will continue to play the for a long time without reinforcement
100
Q

active avoidance definition

A

learning in which an individual must perform an action to avoid a noxious stimulus

101
Q

Mouse placed in a box, warning bell sounds, brief pause, then receives a mild foot shock, learns to escape shock by moving to other side of box when it hears bell

Mouse removed from the box then returned after some time and “tested” for strength of association between bell and foot shock

What is this an example of?

A
  • Strength of memory decreases as interval between training and testing increases
  • Strength of memory increases as strength of foot shock during training increases

Active avoidance

102
Q

Extinction mouse example

A

If mouse hears warning bell and receives no shock several times, will no longer move to the other side of the box

103
Q

How is extinciton different from forgetting?

A

Extinction: “unlearning” an association or learning a new association; disappearance of learned response when response is no longer reinforced

forgetting : decay of a memory or the inability to retrieve a stored memory

104
Q

What example of associative learning are pavlov dogs?

A

active aviodance- extinction

Dogs first learned the association between the bell and the food reward. When Pavlov rang the bell many times without
bringing food, the dogs gradually stopped salivating at the sound of the bell

105
Q

Passive avoidance definition and mice example

A

animal must learn to suppress a behavior that would otherwise be exhibited

Mouse placed in a box with a light and dark section, but when mouse goes in the dark section (which it prefers) it receives a foot shock
The next time the mouse is put into the light section, it should avoid entering the dark section if it remembers receiving the shock there before. Mouse inhibits its inclination to enter the dark section of the box and therefore passively avoids the unpleasant stimulus
Length of time mouse stays in the light section indicates the strength of its memory for the unpleasant stimulus

106
Q

how can short term memories be moved to long term memory

A

rehearsing

107
Q

Short vs long term memory

A

short: persists for seconds to minutes; has a capacity of about seven items
long: lasts for days to years and has no upper limit in capacity or retention

ex: remembering a phone number long enough to dial the number but quickly forgetting

108
Q

types of long term memory

A

Procedural (implicit) memory: “knowing how” to perform procedures, generally nonverbal in humans, require longer to establish but easier to retain skill learning, priming, conditioning

Declarative (explicit) memory: “knowing what”, knowing facts, generally verbal in humans, formed and forgotten easily (Episodic memory -things that happened on a timescale//
Semantic memory-facts)

109
Q

how does epinephrine affect memory?

A
  • Enhances memory in a dose- and time-dependent manner
  • Treatment most effective in enhancing memory if given immediately after training on a memory task
  • U-shaped curve to levels of epinephrine: low and high levels of epinephrine impair memory, moderate levels enhance memory
110
Q

Do animals perform better in avoidance tasks when given moderate or mild foot shock?

A

MODERATE!

Epinephrine released when foot shock occurs and potentiates the effects of noxious stimuli

111
Q

What does epinephrine treatment paired with mild foot shocks produce?

A

Learning comparable to moderate foot shocks

mild levels of endogenous + exogenous epinephrine = moderate levels of epinephrine = improved learning

112
Q

Effects of epinephrine on memory: peripheral receptor hypothesis

A
  • Activates peripheral receptors that communicate with the brain- indirect way for epinephrine to modulate neural circuits
  • α- and β-adrenergic (epinephrine) receptor antagonists block effects of epinephrine on memory
113
Q

effect of peripheral adrenergic stimulation

A

amygdala activation to enhance memory formation

Peripheral epinephrine activates neurons in the vagus nerve that travel to the NTS, which projects to LC

LC projects to the amygdala to modulate the memory of emotional experiences by projecting to other brain regions

114
Q

Blocking …………………… prevents the memory enhancing effects of epinephrine case

A

any part of peripheral receptor pathway

115
Q

Subjects treated with β-adrenergic antagonis

Subjects treated with epinephrine or mild cold stress

A

β-adrenergic antagonist: significantly impaired their memory of an emotionally charged story but not an emotionally neutral story
epinephrine or mild cold stress (increases endogenous epinephrine): enhanced memory for emotionally charged stories but not emotionally neutral stories

116
Q

salivary α-amylase (adrenergic activity biomarker) measured in human subjects before and after viewing emotional and neutral images study results

A
  • Endogenous adrenergic activity greatly increased in response to emotional images but not neutral images in some subjects
  • Subjects with increased endogenous adrenergic activity were much better at recalling emotional images when tested a week later
  • Emotionally charged stories and images activate the amygdala, amygdala activation correlated with memory for emotionally charged but not neutral stories and images
117
Q

How can blocking epinephrine receptors still activate amygdala?

A

by increasing glucose

Epinephrine stimulates the release of glucose which can improve learning and memory

118
Q

Glucose logistics

A
  • time- and dose-dependent: greatest effect immediately after training on a memory task
  • Inverted U: moderate glucose enhances memory, high and low glucose inhibit
119
Q

Glucose effect on memory occurs ….. from epinephrine

A

downstream

120
Q

Memory effects of epinephrine can be blocked by ………………………. but ………….. have no effect on memory enhancement by glucose

A

adrenergic antagonists (peripheral receptor hypothesis)

blockers

121
Q

Almost all drugs that enhance learning and memory in humans (nootropics) elevate

A

blood glucose levels and acetylcholine

122
Q

How does blood glucose affect the brain

A

Elevated blood glucose allows more glucose to enter neurons in the brain, allowing neurons to release more of the acetylcholine

Glucose enhances normal amount of acetylcholine release

123
Q

How do rats treated with glucose during a memory task perform?

A

better and have elevated levels of brain acetylcholine

124
Q

human Alzheimer’s patients

A

Acetylcholine-producing neurons deficit

Increased risk of diabetes

impaired glucose metabolism in cortex and hippocampus (memory-associated)

Abnormal insulin levels and reduced levels of brain insulin receptors

125
Q

Glucose effects base on age

A

Elderly, but not young, subjects treated with glucose prior to a simple memory task perform better than controls

Glucose augments memory for challenging tasks in college students

126
Q

Effects of insulin receptors on memory

A
  • Impaired insulin regulation or insulin receptor function (insulin-dependent diabetes in humans) correlates with impaired memory
  • Insulin receptors are present in the cortex & hippocampus
  • Genetic disruption of brain insulin receptors impairs memory in mice
  • Insulin receptor activation in the brain greatly improves neurotransmission in rodents
127
Q

Effects of treating mice with streptozotocin (STZ)

A

destroys insulin-secreting cells and induces diabetes

Tested for passive avoidance learning: STZ treated mice enter the dark component much faster (did not learn to associate it with footshock)

hippocampus have impaired LTP (associated with learning and memory)

128
Q

Morris water maze

A
  • to test spatial memory
  • mice placed in opaque water and must use extra-maze cues to find a hidden platform
  • STZ-treated mice exhibit pronounced deficits in maze
  • STZ-treated, insulin-supplemented mice have normal maze performance
129
Q

insulin supplementation after diabetes onset…….. spatial memory deficit

A

DOES NOT RESCUE

130
Q

…….. insulin treatment rescues LTP, ……. insulin treatment does not

A

immediate
delayed

131
Q

What does acute stress enhance? Rat evidence?

A
  • performance on learning and memory tasks
  • Stress facilitates classical conditioning of eyeblink response in rats, occurs within minutes and persists for days
  • Adrenalectomy blocks stress-evoked facilitation of learning: glucocorticoids are necessary for learning enhancement due to stress
132
Q

Two types of receptors for glucocorticoids

A

High-affinity mineralocorticoid receptor (MR)
low-affinity glucocorticoid receptor (GR) - require a lot of glucocorticoids to “activate”

Blocking GR in hippocampus, but not MR, impairs stress induced improved performance on eyeblink conditioning task and spatial memory task

GR knockout mice exhibit profound memory deficits

133
Q

Rats that receive a foot shock prior to testing on the Morris water maze

evidence

A
  • prior to testing: perform poorly (take longer to locate the hidden platform)
  • Time dependent: rats shocked 30 minutes before testing do much worse than rats shocked 2 minutes before or 4 hours after testing
  • Foot shock results in elevated glucocorticoid concentrations in about 30 minutes

Acute stress and glucocorticoids may improve encoding and long-term storage of memories, but

134
Q

How does chronic stress (restraint stress) affect performance on radial arm maze?

A

impair performance

Tests both long-term memory (which arms have I learned from previous trials always have food?) and short-term memory (which arms have I already visited in this trial?)

Rats with highest [glucocorticoids] exhibit the most errors in performance

Glucocorticoid receptor antagonist injected into the hippocampus improves performance

135
Q

Chikadees spatial memory

A

rely on spatial memory to find the hidden caches. ability to locate these caches is critical when the food supply is low/unpredictable

when maintained on an unpredictable food supply:
-exhibited moderately elevated glucocorticoid levels compared to those with unlimited access to food
-more efficient at cache recovery and had enhanced spatial memory

136
Q

What can improve cache recovery and spatial memory?

A

glucocorticoid implants

137
Q

how do challenging environments affect spatial memory?

A

moderately increase glucocorticoid levels, which enhance spatial memory

138
Q

how does estrogen affect spatial memory? Morris water maze result

A

enhances memory when the task is particularly difficult: Morris water maze relocated frequently, or a “break” between trials in the radial arm maze

Estrogen particularly enhances “working” (short-term) memory but can sometimes impair “reference” (longterm) memory

139
Q

Evidence in rats that estrogen enhances learning

A
  • Castrated male rats normally perform the same on the radial arm maze as castrated rats implanted with estrogen capsules
  • If rats were forced to wait 1 h in the middle of the task, estrogen-implanted rats are much more likely to visit a baited arm
140
Q

Treating ovariectomized female rats with estrogen for 30 days then removing estrogen prior to testing…..

A

still improves performance on radial arm maze

141
Q

Estrogen injected in ovariectomized rats immediately after training
vs
Injected hours after training

Conclusion

A
  • Immediately after training: enhances memory for the Morris water maze
  • Hours after training: no effect
  • Hippocampus neuron estrogen receptor activation increases dendritic spine density, spine maturation, LTP, and spatial memory

Chronic estrogen treatment induces lasting changes in neuron function

142
Q

How do androgens affect learning and memory in non-human animals?

A

Androgens have little effect on learning and memory: organized, but not activated

143
Q

How do androgens affect learning and memory in animals?

A
  • Androgens have little effect
  • Testosterone replacement therapy has little or no effect on memory task performance
  • Castration has subtle effects on spatial learning
144
Q

What is a possible reason why androgens have little effect on learning and memory?

A

Androgens may be necessary for more “complicated” types of memory mediated by cortex instead of hippocampus such as novel object recognition

145
Q

Between male and female which:
learn active avoidance faster

learn passive avoidance faster

more active

Make more correct choices and fewer errors on a radial arm maze task

A

female: active avoidance faster, more active

males: passive avoidance faster, perform better on spatial learning; Make more correct choices and fewer errors on radial arm maze task (both long-term and short-term memory)

146
Q

Evidence that sex differences in spatial memory organized early in development

A

Castrated males treated with estrogen or testosterone early in life learn radial arm maze faster than female rats/ castrated male rats

147
Q

What do female/feminized male and males/maculinized female rats need to solve the maze?

A

Females and feminized males: both cues inside the maze (landmarks) and cues outside the maze (geometry)

Males and masculinized females: only needed geometry (fewer total cues)

148
Q

Female rats have higher …….. but response magnitude ……. to males

A

higher levels of basal glucocorticoids and stress-induced glucocorticoids

response essentially equivalent to males

149
Q

Male vs female rats- What improves/impairs performance on spatial and visual memory tasks

A

Male: acute stress improves; chronic stress impairs

Female: acute stress impairs; chronic stress improves or has no effect

150
Q

Evidence that sex differences in learning and memory due to stress is organized early in development

A

male: androgens organize the brain to enhance learning when adults experience acute stress

female: lack of androgens results in impaired learning when adults experience acute stres

Chronic stress-induced increases in glucocorticoids associated with impaired memory in human men, but not women

151
Q

How does chronic stress differentially affect male and female brains?

A
  • Reduces dendritic branching and dendrite lengths in hippocampal neurons in males; no reduction in females
  • Can be prevented by blocking glucocorticoid release or glucocorticoid receptor
  • psychosocial reduces hippocampal neuron number in male, but not female, non-human primates
152
Q

Evidence that acute stress differentially affects the brain in males and females

A

increases spine density in males but decreases spine density in females

Female rats in proestrus (high estrogen) have higher density of dendritic spines on hippocampal neurons than males

153
Q

Acute stress-evoked changes in hippocampal neurons

A

temporary and can resolve several days after the stressor stops (takes longer for chronic stress)

154
Q

Melatonin: white-footed mice winter vs summer days

A
  • “winter” (short day) nice require longer to learn the Morris water maze than those in “summer” (long day) photoperiods
  • “Winter” mice have smaller total brain size, smaller hippocampus volume, decreased hippocampus neuron dendritic spine density
  • Winter photoperiods lead to increased duration of endogenous melatonin release
  • Melatonin implants mimicking amount of melatonin released during winter in mice housed in “summer” photoperiods has the same effect as “winter” photoperiod
155
Q

Where can melatonin receptor found?

A

throughout hippocampus

156
Q

What rats learn memory tasks much slower than controls?

A

Adrenalectomized or hypophysectomized (removed pituitary) rats

157
Q

What restores learning in adrenalectomized and hypophysectomized rats

A

ACTH (unclear how ACTH reaches the brain since it cannot cross the BBB)

158
Q

ACTH

A

Can act as an antiamnestic (protects against forgetting): protein synthesis inhibitor treatment after training causes amnesia, but when given with ACTH amnesia is reduced

Does not seem to directly affect learning and memory in humans but instead increases overall arousal, attention, and motivation

Biol 405: Comparative Endocrinology (5 decks)

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