Neuro 4 Flashcards
stress
reaction to harm or threat
stressors
stimuli that cause stress
acute stress
stressor that is sudden and short term
chronic stress
stressor is ongoing and long-term
are stressors physical or psychological
both
Hans Selye
coined the term ‘stress’. he was an endocrinologist.
first he said stress is “the nonspecific response of the body to any demand made to it” -> emphasized the body’s physiological reaction to various stressors, regardless of whether they were physical, emotional, or environmental.
later he said “stress is not what happens to you but how you react to it” ->This highlighted the role of perception and individual response in determining the effects of stress on health.
chronic psychological stress
most clearly linked to ill health. In the short term, stress is adaptive, in the long term it is maladaptive.
eustress vs distress
good stress vs bad stress
when a stressor occurs, what happens in the brain- two system view
- HPA system
- Sympathetic nervous system
HPA system (function + neural circuitry)
The HPA system (Hypothalamic-Pituitary-Adrenal axis) is a key part of the body’s stress response. It uses hormonal and neural signaling.
Order:
Hypothalamus -> Anterior Pituitary -> Adrenal Cortex -> Glucocorticoids
sympathetic nervous system pathway
sympathetic nervous system->adrenal medulla-> makes and secretes norepinephrine and epinephrine
stress response immediate
Sympathetic nervous system (SNS)
- works through neural mechanisms
- matter of seconds
Delayed stress response + process
The HPA axis is a central stress-response system involving both neural and hormonal mechanisms.
PROCESS
1. Neural and Hormonal Initiation:
hypothalamus activates and releases corticotropin-releasing hormone (CRH) into the bloodstream.
- Pituitary Activation:
CRH travels to the anterior pituitary, where it stimulates the secretion of adrenocorticotropic hormone (ACTH).
ACTH is then released into systemic circulation. - Adrenal Cortex Activation:
ACTH binds to receptors in the adrenal cortex. This triggers the synthesis and release of cortisol.
Hypothalamic pituitary adrenocortical
HPA
glucocorticoids
stress hormones produced/released by the adrenal gland during stress response. Particularly dense in the hippocampus.
Biological assessment of stress- SNS
ways to measure the biological assessment of stress via the Sympathetic Nervous System (SNS):
- norepinephrine and epinephrine levels - galvanic skin response - heart rate - blood pressure - salivary alpha amylase levels
Biological assessment of stress-HPA
cortisol/corticosterone levels
TSST
Trier social stress test.
- give speech and suddenly take away notes at last minute. judges force them to continue to the full time slot
experiment using Tsst
administer DEX (synthetic glucocorticoid) to block HPA acute response
administer PROP(beta blocker) to block SNS stress response
- DEX Group (Blocking the HPA Axis Response):
Old Findings:
In earlier studies, DEX effectively suppressed the HPA axis response, preventing the cortisol increase typically seen during stress.
Subjective stress ratings were lower, likely because cortisol suppression minimized the perception of physical stress signals.
New Findings:
Even in the DEX group, a smaller cortisol peak occurred before the presentation, though it was significantly lower than the placebo group.
Interestingly, the DEX group reported higher subjective stress compared to the placebo group before the presentation.
- PROP Group (Blocking the Sympathetic Nervous System Response):
Cortisol Findings: The PROP group showed higher cortisol levels than the placebo group, which is counterintuitive given that propranolol blocks the SNS (e.g., heart rate, blood pressure).
Subjective Stress Findings: Despite the physiological difference, there was no difference in subjective stress between the PROP and placebo groups.
how do we measure stress
self report
GSR (galvanic skin response)
heart rate
levels of cortisol or corticosterone in saliva or blood
Is self reported stress accurate
no, not always
circaidan rythmn and stress
Cortisol levels naturally rise at the end of the sleep period.
This increase is part of the body’s circadian rhythm and is not necessarily an indication of “stress” in the psychological sense. Instead, it reflects the body’s preparation for waking and starting the day, providing energy and alertness.
However, this rise can feel like stress if other factors are present, such as:
Chronic Stress: If someone is under ongoing stress, cortisol levels may be elevated even during sleep, leading to a heightened or dysregulated CAR. This can manifest as waking up feeling anxious or on edge.
Anticipatory Stress: If someone is dreading an upcoming event (e.g., a big presentation or test), the cortisol peak may be amplified, and they might interpret this as stress upon waking.
physical stressors (physiological/systemic)
disdurbance of physiological status that overwhelm specific hemoestatic mechanisms
- i.e. infection
- i.e. hemorrhage
psychological stress
involves stimuli or conditions that challenge an organism’s ability to maintain its current or anticipated homeostatic state.
Types:
threats to organisims current or anticipated state
social conflict
aversive environmental stimuli
stress tests for animals
inescapable footshock
restraint
forced swim
social defeat (small rat with big rat)
Study -how were rat stressed (5 groups) and what were results
Physical stressors
- hemorrhage
- immune stress
Psychological stressors
- restraint
- noise
Other stressor (difficult to categorize)
- forced swim
Then measured Fos expression in various brain regions that was induced by exposure to different stressors
RESULTS
- looked in PVN (paraventicular nuclues of the hypothalamus) for CRF (corticotropin releasing factor) - no change.
- looked in the medial nucleus of amygdala(MeA) and central nucleus of amygdala (CeA) - found physical stressors were in Central amygdala and psychological stressors (+ swim) in the medial nucleus of amygdala
so does the amygdala pass info about stressor onto hypothalamus?- Experiment to test this
neurotoxic lesion
- amygdala central nucleus
- amygdala medial nucleus
psychological stressor
- restraint
measure for Fos expression in PVN hypothalamus
Results-
- medial amygdala needs to be intact to be able to see a stress induced increase in Fos in the hypothalamus PVN. so are they communicating directly or indirectly?
Then they did double labelling. injected retrograde tracer into PVN- tracer will pack label neurons. Then they assessed amygdala sections- cells showing both Fos and tracer are cells that were activated by stressor (fos) and also project directly to PVN (tracer)
Results- found very few double labelled cells, so the MeA neurons that project to PVN are not the same neurons activated by the stressor itself. this suggests an indirect communication (I.e. goes from MeA to another area to the PVN. theory- maybe the place would be the BNST- bed of neuclues of straia terminalis)
what is sexually rewarding to female rat
paced copulation
paced copulation
females ability to control initiation and rate of copulation
passed copulation supports a conditioned place preference in female rats
female rats will also selectively approach, solicit and have sex with make rats that bear an odor associated with paced copulation (odor is functioning as CS)
paced copulation box
area where female rat can enter male rat’s area if she wants to
paced copulation pavlovian experiemtn
experimental group(odor paired)- paced copulation with a rat that smells like almond and then normal with a rat that is unscented. control group (odor unpaired)- swapped. paced is with unscented rat, nonpaced is with scented.
test- present odor of CS (almond) by itself to the rat. then wait 60 minutes and collect brain for Fos training. found more activation in piriform cortex, mPOA and ventral tegmental area for odor paired group.
Activated regions included:
Piriform Cortex: A region associated with odor processing and olfactory memory.
Medial Preoptic Area (mPOA): Critical for sexual motivation and copulatory behavior.
Ventral Tegmental Area (VTA): A key region for reward and reinforcement learning.
Same odor/stimulus can induce different brain activity based on meaning.
the odor aquired meaning in the brain because it was associated with a positive experience.
pituitary gland-
often referred to as the “master gland”- regulates many bodily functions by releasing hormones that control other endocrine glands.
It is specifically the anterior pituitary that earns this title because it produces and releases tropic hormones, which influence the activity of other glands.
neural control of pituitary
The hypothalamus regulates the anterior pituitary through hormonal signaling, rather than direct neural connections, which distinguishes it from the regulation of the posterior pituitary. (established via stimulation and lesion experiments )
posterior pituitary(neural input, hormones)
receives direct neural input from the hypothalamus.
Releases two major hormones
- vasopressin
- oxytocin
(both involved in stress responses and social bonding)
These are peptide hormones synthesized in bodies of neurons located in the periventricular nuclei and supraoptic nuclei of the hypothalamus
terminals of these neurons in posterior pituitary
- arrival of action potential at the axon terminal causes hormone release into bloodstream
vasopressin
antidiuretic hormone- facilitates water reabsorption by kidneys and can be involved in stress
oxytocin
stimulates uterine contractions during labor and milk ejection during breastfeeding
anterior pituitary
The anterior pituitary functions as part of the hypothalamic-pituitary axis. hypothalamopituitary portal system carries hormones from hypothalamus to anterior pituitary
first functional sex difference discovered in the mammalian brain
Gonadectomy in Neonatal Rats:
Neonatal gonadectomy (removal of gonads) in either male or female rats caused them to develop a female cyclic pattern of gonadotropin release (regulated by the hypothalamus).
This implies that the default developmental trajectory is to establish a female-like hormonal rhythm unless influenced by factors such as testosterone.
Gonad Transplants:
Transplanting testes into neonatal female rats caused them to develop the male steady-state pattern of gonadotropin release in adulthood.
Ovary transplants into gonadectomized neonatal rats (male or female) did not alter their hormone release pattern. They retained the cyclic female pattern unless testosterone was present.
Conclusion:
The presence of testosterone during the perinatal period (critical developmental window) masculinizes the hypothalamus, programming it to adopt the male steady-state pattern of gonadotropin release.
In the absence of testosterone, the hypothalamus develops into its default state, which supports the female cyclic pattern of gonadotropin release.
release of gonadotropin
from the anterior pituitary, controlled by the hypothalamus
aromatization hypothesis
perinatal testosterone does not directly masculinize the brain. rather, the brain is masculinized by estraioal that has been aromatized from perinatal testosterone.
aromatization hypothesis - WHY
early estradiol injections masculinize the brain.
androgens that cannot be aromatized to estradiol do not masculinize the brain
testosterone administered with chemicals that block aromatization does not masculinize the brain
how are genetic females ‘protected’ from estradiol masculinization
in utero, fetuses will be exposed to other estradiol through the blood supply. alpha fetoprotein’protects’ the genetic females. it is present in the blood of rats during the perinatal period. binds to circulating estradiol and ‘deactivates’ it (binding prevents transport across the lacenta)
alpha fetoprotein and genetic males
testosterone is not impacted by alpha fetoprotein. testosterone travels from testes to the brain and in the brain it is converted to estradiol. Alpha fetoprotein does not cross the blood-brain barrier
hormones (3 types)
3 types:
1. amino acid derivatives (epinephrine)
2. peptides and proteins
3. steroids
epinephrine (acting as a hormone)
released from the adrenal medulla. synthesized from tyrosine.
peptides and proteins
short and long chains of amino acids
steroids
synthesized from cholesterol, fat soluable and able to enter cells + bind to receptors in cytoplasm or nucleus. able to directly influence gene expression.
sex hormones (I.e. androgens, estrogens, progestogens)=steroid hormones
organizational effects
developmental. relatively permanent effects of hormones on structure + function (body+ brain). does not preclude effects on behavior
critical development period
- fetal development and prenatal period (hormones lay down foundations) , during puberty (can activate or suppress sexual behavior that was developed in previous 2 phases)
activational affects
usually reversable effects on already developed neurons. think of it as a switch mechanism- can activate or suppress. can also be triggered by environmental cues (I.e. birds length of day changes/cues hormone levels)
human brain, development, and hormones
human brain is slow to develop- hormones may surge during puberty before full development.
organizational examples
formation of reproductive hormones
formation of neural circuits/regions in the brain. (ie medial preoptic area)
activational examples
menstrual cycle and reproductive behavior.
elevated estrogen in rats
rapid increase in lordosis
female human sexual behavior (estrogen)
increase in female-initiated sex before ovulatory phase (when estrogen is higher) - 3 day window ish
queer women- same thing. means that evolutionarily sex is selected when pregnancy COULD be possible
Castration of rats
removal of male rat testes leads to decrease in neural size and dendritic branching within medial amygdala. testosterone treatment in adulthood can reverse this though.
Phoenix et.al. (TT vs TE study)
Experiemental- injected pregnant guinea pigs w testosterone
Control group
overariectomized female offspring before puberty to prevent natural hormone effects in adulthood. then studied behavior (males- mounting, females- lordosis)
injected some w testosterone as adults and others w estradiol and progesterone (both known to put animals in heat) as adults.
RESULTS:
- TT group had most mounting, TE group had least lordosis
- Thus, prenatal testosterone (T) masculinized AND defeminizes
- Castration males(the C males without testosterone)- feminized and demasculinizes.
- So long term changes in hormonal behavior begin in the brain.
study lab graphs
NOW
precopulatory phase- male
sniffing(genital area of other rat)
chasing
producing ultrasonic vocalizations
copulatory phase: 3 distinct behaviors- male
mount, intromission, ejaculation
mount latency
time that elapses between introducing the male and female to the test apparatus before the male first mounts the female
intermount interval
time between successive mounts
intromission latency
time that elapses before first intromission
inter-intermission interval
time between successive intromissions
ejaculation latency
time taken to reach ejaculation
post ejaculatory interval
time elapsing between ejaculation and next mount or intromission
pre-copulatory phase- female
- approach, nuzzle, sniff
- solicitations (headwise orientation toward male and then run away. both look at each other. then she runs and he chases)
- widdle ears
- hops
- darts
copulatory phase- female
lordosis
appetitive
(sexual motivation)
variable sequence of behaviors that involves attracting and courting a mate
- locomotor excitement
- investigative behavior
-things they do to get close to each other (preparation for consummatory contact)
consummatory
(copulatory behavior- highly stereotyped)
- the sex itself
conditioned place preference - CPP
two compartments. stripes of different orientations and different flor textures. Pair one compartment with rewarding experience and prepare the other without. In this case, reward is sex. Then allow to move throughout- where do they spend the most time. If they spend time in reward side, then they are having appetitive behavior of seeking sex.
electric grid test- runway task
runway. put subject on one end and sexually receptive rat on the other end. There is an electric grid in the middle. Is rat willing to run through an aversive experiment for sex?
conditioning chamber with rats for sexual behavior
rats have sex in chamber with a cue light that gets associated as a cue for sex. Then male gets to lever press to turn on cue light, which cues that sex is coming. This light gets rat to keep pressing and eventually it opens the door for the other rat to enter.
appetitive- lever press
effects of mPOA lesions on consummatory male sexual behavior
copulatory : medial preoptic area lesions cause a massive decline in mounting and intromission and cause NO ejaculations
POA and AMY on copulatory vs appetitive behavior
Appetitive- appetitive behavior (pressing lever) when BLamygdala is in tact. When not in tact, it decreases. POA had no impact.
copulatory- when POA is in tact, copulation occurs. When not in tact, it decreases. BLAmygdala had no impact.
caveat to BLA in sexual behavior
role of BLA is not specific to appetitive sexual behavior, its just broadly implicated in appetitive behavior in general.
Likely- BLA lesioned rats have trouble associating cues with its motivational value.
dopamine in sexual behavior - nucleus accumbens
dopamine is heavily implicated in sexual reward.
In the nucleus accumbens:
- when the male is placed into the chamber where he has mated previously (anticipatory)
- dopamine increases further when the male can see the female but not contact her(anticipatory)
- then even more when he is able to mate
not unique to sexual reward - similar in other kinds of reward too
glutamate POA (anticipatory)
no increase in glutamate release in mPOA during the anticipatory phase (in the presence of an inaccessible female).
glutamate in mPOA
modulate consummatory aspects of sexual behavior. seems to modulate both appetitive and consummatory aspects of male sexual behavior. link to responses not simply associated with mounts, intromissions and ejaculations (copulation itself)
