What evidence exists showing that maternal behavior is mediated by hormones quizlet?

Hormones: Thyroxine, T3, T4
Fx: Metabolism, Growth and development, located in neck wrapped around vocal chords, increase oxidation rate of glucose in cells, can store hormones, Need carrier protein, lipid soluble hormones, stimulated by anterior pituitary, uncouples oxidative ATP

Advantages: Study lifespan changes, wider range of studies (ethics), bigger sample, less expensive, ease of replication & quantification, environmental control
Disadvantages: Abstraction and Bias, anthropomorphizing, relevancy of behavior, correct description of behavior, hard to determine "normal behavior", No motive attribution

Peptide hormones: Short chain of Amino Acids ex. glucagon, insulin, leptin. Stored in endocrine cells and released via exocytosis, do not require carrier proteins, shorter half life, water and blood soluble.

Steroid Hormones: Require carrier protein, larger, fat soluble, unique carbon structure, synthesized from cholesterol, not stored in cells, longer half life. Ex. Progesterone, testosterone, estrogen, cortisol, aldosterone

Brain activity- fMRI, EEG, Electrodes, in vivo electrode physiology
Neuroanatomy- dissection, MRI, PET, CT, IHC, ICC, Bioassay
Behavior- Humans and other animals (monkeys, rats, etc.)
Sex differences: SDN-POA, BNST, SCN, Corpus collosum, MPOA, POA

A. Altricial, precocial, semi-precocial
B. Precocial, altricial, semi-precocial
C. Semi-precocial, altricial, precocial
D. Precocial, semi-precocial, marsupial

Answer: B. Precocial, altricial, semi-precocial

Sets with similar terms

What is parental behavior?

Any behavior that contributes directly to the survival of fertilized eggs or offspring that have left the body of the female

What are the types of parental behavior?

Maternal: mother, most common among mammals (90%)
Paternal: father
Biparental: both mother and father, rare among mammals (10%) but common in birds
Alloparental: individuals who are not the biological parents, e.g. siblings

What type of parental care is most common in birds?

biparental

What type of parental care is most common in mammals?

maternal

Why Parental Behavior?

From an evolutionary perspective, mating is not sufficient for reproduction to be successful

Parental care is critical for reproductive success

Parental care is critical for reproductive success
What is reproductive success determined by?

Determined by their offspring that manage to survive and produce descendants
One or both parents must take care of helpless offspring so the offspring can survive to maturity so that they can reproduce themselves

How do parents maximize fitness?

To maximize fitness, the optimal strategy for each parent is to provide sufficient care but no more than is necessary to produce successful offspring

The amount of care a parent provides varies greatly within and among species

Some species provide little or no parental care:
examples

Cowbirds
Brown trout
Female Nile crocodiles

Cowbirds

Nest parasites
Deposit their eggs into nests of other birds
Adoptive parent provides parents care (incubating eggs, feeding, protect hatchlings)

Brown trout

Females simply release hundreds or even thousands of eggs from their bodies
The eggs remain where they fall
No parental care is provided
Sheer number of eggs released ensures that some offspring will survive

Female Nile crocodiles

Provide a low level of parental care: build nests and protect their newly hatched young by carrying them to the water in their mouths.
Most other reptilian species merely cover their newly deposited eggs with dirt and provide no additional parental assistance

What are altricial offspring?

(e.g. dogs, rats)
Large numbers of immature and helpless young, that require significant amounts of care
However, some species that that do not provide parental care to their altricial young can simply rely on the production of large numbers of offspring to ensure that at least a few will survive.

what are precocial offspring?

(e.g. sheep, deer, guinea pigs)
Few well developed offspring that show high degree of independent activity
May be able to survive with little or no parental intervention
In many species that bear prococial young, an exclusive bond forms between mother and young soon after birth

what are semi-precocial offspring?

(e.g. humans and other primates)
Helpless and demand significant attention at birth but can cling to the mother

Rat maternal care

Rats have a 22 day gestation period (pregnancy)
After delivery (parturition), the pups remain with the mother until the time of weaning ~3 weeks later.
During this time, mother rats (dams) display many caregiving activities.

What are the components of rat maternal behavior during gestation?

Nest building
Rats have a 22 day gestation period (pregnancy)

What are the components of rat maternal behavior during parturition?

Lick and groom area around the vagina and assist with uterine contractions by pulling pups out with the teeth
Clean fetal membranes off pups
Placentophagia

What are the components of rat maternal behavior after birth?

IMMEDIATELY AFTER BIRTH, mothers (dams) are maternal and display behaviors necessary for altricial young to survive:
Hovering over pups
Arched-back nursing (ABN)
Licking and Grooming (LG)
Retrieval
Grouping
Aggression to defend the nest and protect pups from predators

What is placentophagia? What are hypotheses as to why animals engage in this practice?

Placentophagia (Kristal et al., 2012) - when the mother rat eats the placenta and umbilical cords of all the pups. Why?
Keeps the nest area clean and reduces odors that would attract predators?
Replenishes nutritional loss from pregnancy?
Way to self medicate (i.e. opioids) ?

Placebo-controlled studies assessing the effects of placentophagy for postpartum recovery and health are needed to help elucidate any positive or negative effects

What hormones regulate the immediate onset of maternal care at parturition (birth)?

prolactin and estradiol increase greatly after parturition
progesterone decreases post birth
High E+PRL coupled with low P is the switch that triggers maternal care

How do concentrations of these hormones change across gestation (pregnancy) and at parturition?

Estradiol: is low throughout the entire pregnancy and spikes up a couple days before parturition, takes a dip down on day 22 and then spikes up even higher than before right after parturition
prolactin: low throughout pregnancy, spikes up a day before parturition and that spike keeps on dramatically increasing after parturition
progesterone: high during insemination, low after insemination, spikes up again at day 5, gradually increases until day 16, and then goes completely down by the time of parturition

What are two approaches that have been used to show that hormones regulate the onset of maternal behavior?

1) Foster pups are presented to adult females in different endocrine states. Whether and how quickly these females begin to behave maternally is measured.
2) Pregnancy termination by hysterectomy (removal of the uterus, fetuses, and placenta) on days 16-19 pregnancy

1) Foster pups are presented to adult females in different endocrine states. Whether and how quickly these females begin to behave maternally is measured.

Hormones significantly reduce the amount of time it takes for a virgin female to behave maternally and therefore promote maternal care

2) Pregnancy termination by hysterectomy (removal of the uterus, fetuses, and placenta) on days 16-19 pregnancy

Results in maternal behavior towards foster pups within 1-2 days
Produces similar endocrine profile to that found in a normal rat just prior to birth
Removal of placenta main causative factor. Why?
Placental lactogen (PL) supports corpora lutea which produces progesterone: Removal of placenta → PL decreases → regression of corpora lutea → progesterone decreases
Chorionic gonadotropin (CG) suppresses estrogen production: Removal of placenta → CG decreases → no suppression of ovarian estrogen → estrogen increases prolactin increases

Hormonal profile of late pregnancy stimulates the onset of maternal care

What is maternal sensitization or concaveation?

when mothers learns to care for pups

nulliparous females are fearful of pups at first but after 5-6 days of exposure they behave maternally

- Hormones significantly reduce the amount of time it takes for a virgin female to behave maternally and therefore promote maternal care

How long does it take the following groups to behave maternally when presented with foster pups: new mother, late pregnant female, virgin female, virgin female transfused with blood of new mother, OVX virgin female treated with a hormonal regimen that mimics changes seen during late pregnancy?

Mothers that have recently given birth: immediately

Late pregnant: 1-2 days

Nulliparous (virgin): are fearful of pups and find them (odors) aversive
Will avoid or attack pups on first day of exposure but...
After > 5-6 days of pup exposure, they behave maternally (maternal sensitization or concaveation: when mothers learn to care for pups have exposure)

Nulliparous females transfused with blood from a new mother: 1 day

Nulliparous females that are ovariectomized and treated with a hormonal regimen (E+P+PRL) that mimics changes seen during late pregnancy: 1-2 days

how long does it take female rat with previous maternal experience?

female with maternal memory will display maternal behaviors to pups within one day

How long does it take pregnant rat hysterectomized on days 16-19 of pregnancy?

Results in maternal behavior towards foster pups within 1-2 days
Produces similar endocrine profile to that found in a normal rat just prior to birth

Be able to explain why and how hysterectomy induces maternal behavior.

Produces similar endocrine profile to that found in a normal rat just prior to birth
Removal of placenta main causative factor. Why?
-Placental lactogen (PL) supports corpora lutea which produces progesterone: Removal of placenta → PL decreases → regression of corpora lutea → progesterone decreases
-Chorionic gonadotropin (CG) suppresses estrogen production: Removal of placenta → CG decreases → no suppression of ovarian estrogen → estrogen increases prolactin increases

Hormonal profile of late pregnancy stimulates the onset of maternal care

Does oxytocin act as a hormone or neurohormone to: facilitate maternal behavior? uterine contractions? milk ejection?

Oxytocin peripherally (hormone):
-Uterine contractions during childbirth
-Milk ejection

Oxytocin centrally (neurohormone):
-Injection of OT into the brain of estrogen-primed nulliparous females leads to a rapid onset of maternal behavior within 1 day
-Central administration of an OTR-A prevents the onset of maternal behavior as do lesions of PVN , area of the hypothalamus is the source of OT in the brain

How do hormones promote maternal behavior?

Approach-Avoidance Model:
Increase attraction/approach to pups by making them rewarding
-Mother rats will bar press to get pups, cross electrified grids
Reduce natural fear and avoidance of pups (odors)

**why do the stimulatory effects of hormones on maternal behavior diminish after a few days?

Latency to display maternal behavior towards foster pups measured in pregnant females at various time points after C-section:
-C-section on day 22 of pregnancy and presented with foster pups 1-3 days later = 1 day
-C-section on day 22 of pregnancy and presented with foster pups 8-10 days later = 6-8 days
-Virgin female = 6-8 days

Hormonal events of pregnancy termination result in heightened maternal responsiveness for just a few days

Is the maintenance of maternal behavior dependent on hormones? What is the evidence? If not, what maintains maternal behavior?

Some hormones (i.e. oxytocin) may continue to play a role in modulating the quality and quantity of maternal care but hormones are not necessary to maintain maternal behavior during the remainder of the postpartum period

Instead, the maintenance of maternal behavior depends on pup stimulation (i.e. somatosensory or tactile feedback that a dam receives from the pups)
- Anesthetizing or severing the nerves that innervate the mouth --> nest building, licking and pup retrieval abolished
- Anesthetizing the mother's nipples --> failure to nurse pups

Behaviors that maintain maternal behavior:
- distal cues: of sight and sound stimulate contact seeking
- perioral contact of touch from mother to pup stimulates nuzzling, licking and hovering over
-ventral contact of the touch from pups to mothers stimulates crouching posture which stimulates suckling

Hormones induce maternal care but pup interactions maintain it

**Somatosensory and tactile feedback that a dam receives from the pups is necessary to maintain maternal behavior

- Anesthetizing or severing the nerves that innervate the mouth --> nest building, licking and pup retrieval abolished
- Anesthetizing the mother's nipples --> failure to nurse pups
Hormones induce maternal care but pup interactions maintain it

**what are the interactions btw mother and pup that maintain behavior?

- distal cues: of sight and sound stimulate contact seeking
- perioral contact of touch from mother to pup stimulates nuzzling, licking and hovering over
-ventral contact of the touch from pups to mothers stimulates crouching posture which stimulates suckling

Understand the neural circuitry of maternal behavior, particularly the role of the MPOA in early to mid pregnancy

MPOA inhibits circuit that promotes aversion to pup odors
Lesioning other parts of aversion circuitry (i.e. MeA, PAG) also abolish the aversion of virgin females to pups

AVOID: pup odor activates olfactory bulb --> Medial and cortical amygdala --> Anterior hypothalamus and the Periaquiductal gray --> causes aversion to pups

Understand the neural circuitry of maternal behavior, particularly the role of the MPOA in late pregnancy

Na --> PVN --> triggers oxytocin release --> goes into the oxytocin receptors of the mPOA --> stimulates MPOA which activates
GABA and sends it to the meA and CoA and PAG to inhibit the avoid response and sends glutamate to the NAcc and VTA to activate the reward response
During this phase, there is a rise in prolactin and Estrogen, and a decrease in progesterone

Understand the neural circuitry of maternal behavior, particularly the role of the MPOA in lactation

APPROACH

Maternal care is disrupted when 1) interfere with DA neurotransmission 2) disrupt the connection between the MPOA and VTA
DA agonists into the NAc can stimulate maternal responsiveness even without hormones.

MPOA activates circuit that enhances approach/attraction to pups
(i.e. mesolimbic DA system involved in motivation and reward)

the VTA and NAcc interact with each other and create DA which leads to maternal behavior, rewarding, and motivation.

MPOA and Maternal Behavior

Neural activity in the MPOA (as measured by c-fos) increases in dams

Lesions of MPOA disrupt maternal behavior

Has receptors for E, PRL and OT which increase in number during pregnancy to maximize sensitivity
In postpartum females, blocking receptors for these hormones in the MPOA will disrupt maternal behavior
In virgin females, infusion of these hormones into the MPOA will induce maternal care

What about pups do adult nulliparous rats find aversive? How can this aversion be overcome?

the odor
Latency to maternal behavior is reduced by making virgin females anosmic
-without the ability process olfactory stimuli (anosmic) from pups , females exhibit maternal behavior almost as quickly as new mothers.
Lesioning other parts of aversion circuitry (i.e. MeA, PAG) also abolish the aversion of virgin females to pups

What is maternal memory? What does it reveal about the hormonal regulation of maternal behavior?

1. Previous experience as a mother ("maternal memory")
Females that have given birth and allowed to interact with their pups will later display maternal care towards foster pups within 1 day regardless of their current hormonal status
As little as 30 min of interaction is sufficient to facilitate her future maternal responsiveness
Hormones are important for priming first time mothers to behave maternally but maternal experience can render future maternal behavior less dependent on hormones
2. Own experience of being mothered as an infant
The amount of licking/grooming/arched back nursing a female rat pup receives can directly affect her own mothering as an adult

• How has it been shown that maternal care affects the maternal care of female offspring? What is affected? Are these effects due to genetic/prenatal factors or differences in postpartum maternal care? How has this been shown?

Own experience of being mothered as an infant
The amount of licking/grooming/arched back nursing a female rat pup receives can directly affect her own mothering as an adult

Individual variations in maternal care are transmitted across generations
-Cross fostering studies show that differences in offspring phenotype are related to the level of postpartum care received NOT genetic or prenatal factors

Individual Variations in Maternal Care are Associated with Differences in Oxytocin Receptor Levels
-Like their mothers, high LGN-ABN offspring have high OTR levels whereas the low LGN-ABN have reduced OTR levels

What is the hormonal profile of pregnancy in humans?

High estrogens and progesterone throughout pregnancy (different than rodents)
Prolactin increases during pregnancy (stimulates mammary glands to produce milk)
Oxytocin increases at birth (smooth muscle contractions during labor)
Increases in ACTH and cortisol throughout gestation (to suppress immune reaction of the mother toward the fetus)

Why is studying hormonal correlates of parental care in humans difficult?

Establishing hormonal correlates of human maternal behavior is difficult:
-Hormone are neither necessary nor sufficient for maternal care (i.e, adoptive parents, grandparents, siblings, other relatives and caregivers)
-Humans have no clear cut universal set of maternal behaviors
-Behavior per se is rarely studied in humans, questionnaires and surveys used

What hormonal changes have been associated with human maternal behavior and how are these hormonal changes thought to promote maternal behavior?

Mothers with an increase in the ratio of estradiol to progesterone during pregnancy have more positive attachment to their infants than mothers with a decrease in the ratio of these hormones

Plasma oxytocin levels at 2 weeks postpartum positively correlated with maternal bonding behaviors (gaze, vocalizations, positive affect, and affectionate touch) as assessed during a 15 min mother-infant interaction (Feldman et al., 2007)-correlational

Handgrip force reaction to infant crying reduced in nulliparous women given intranasal oxytocin suggesting that oxytocin may inhibit parental hostility (Bakermans-Kranenburg et al., 2012)

Mothers with higher concentrations of blood cortisol engage in more physically affectionate behaviors and talked more often to their babies than mothers with low cortisol (Fleming et al., 1987)
Cortisol may increase the mother's general level of arousal and thus increase her responsiveness to infant related cues
New mothers with higher cortisol concentrations find their infants' odors more appealing than do mothers with lower concentrations (Fleming et al., 1997)
Increased approach? Decreased avoidance?

What genetic factors have been linked to individual differences in human maternal care?

Polymorphism in oxytocin receptor gene
-One variant (SNP) that may make the receptor less capable of inducing downstream signaling was associated with lower maternal sensitivity, i.e. reduced ability to accurately perceive children's signals and to respond in an adequate and prompt way

Polymorphism in dopamine receptor 4 gene
-Mothers with certain variants less sensitive to children in face of daily hassles
-Negative parenting behaviors, esp. in disruptive kids (gene x environment interaction)

What are the 4 major systems and the brain regions within those system that fMRI studies have implicated in maternal caregiving?

- Empathy: STS --> IP --> IF (understanding child's facial expression), AI (understand what the child feels)
- Reward and motivation: VTA --> Vstr --> mPOA (motivation to approach offspring)
- Cognitive control and emotional regulation: LPFC (regulating negative reaction to cries)
- Arousal: amygdala (arousal in response to cries)

More isn't necessarily better when it comes to activation of these brain systems. There may be an optimal range of activation of these neural systems -too low (neglectful) or too high (intrusive) may not support adequate parenting.

Paternal behavior is

uncommon and only found in ~10% of mammalian species

Among mammals, what makes it more likely that a male will care for his offspring?

Males care for offspring when they can increase their own reproductive fitness:
Two adults are required to guarantee the survival of the young
Certainty of paternity is very high

Tends to occur in in species that are monogamous

In California mice fathers:
- What parental behaviors do they display?

Exclusively monogamous and form long-term pair bonds

With the exception of lactation, males and females of these species exhibit the same parental behaviors to the same extent

In California mice fathers:
- What is the relationship between prolactin and paternal behavior?

Elevated prolactin levels are associated with paternal behavior in California mice

In California mice fathers:
What is the relationship between testosterone and paternal behavior? Is this common or unusual for mammalian paternal care?

Aromatase inhibitor blocks effects of T suggesting that T promotes paternal behavior through conversion to estradiol

Unusual pattern!

In California mice fathers:
What brain region is part of the neural circuitry underlying paternal behavior?

mPOA is important for parental behavior in male and female California Mice
In both males and females, mPOA lesions increase the latency to display parental behavior

What hormonal changes have been associated with human paternal behavior?

Oxytocin levels associated with greater parental care and more infant touch in fathers

Prolactin increases in fathers prior to birth and in men who respond physiologically to the sounds of babies crying

Testosterone and cortisol also linked to paternal care (Berg & Wynne-Edwards, 2001)
Saliva samples from first time father recruited from prenatal classes compared to controls - general population, matched for age, time of day, season
-found that testosterone was lower in fathers than the controls and cortisol was also much lower in fathers than the controls.

How are the hormonal changes father thought to promote paternal care?

Compare hormonal responses of new fathers and non-fathers exposed to sounds of baby crying
Fathers with low T and low cortisol concentrations felt more sympathy to the infant cries and fathers
Hormonal changes may make fathers more empathetic to infant cues

What do fMRI studies suggest about the neural basis of human paternal care?

fMRI studies show that when a father hears his own child's cries, areas of heightened brain activity include the include the frontal cortex, insula, thalamus and superior temporal cortex (Swain, 2008) - same as mothers

Difference: brain activity patterns don't change as quickly for fathers as they do for mothers

What did the study looking at the relationship between paternal care and testicle size show?

(Mascaro et al., 2013)
Activity in the ventral tegmental area (in response to viewing photos of their own children)—a key component of the mesolimbic dopamine reward and motivation system—predicted paternal caregiving and was negatively related to testes volume.

Other primates:
Male chimpanzees, which are especially promiscuous, have testes that 2x bigger than humans, make a lot of sperm and generally do not provide paternal care.
Male gorillas have relatively small testes and protect their young.
These data in humans may at least partially explain why there is large variability in quality of care that fathers provide and why some men are dedicated sensitive caregivers and others are completely absent.

• What two general categories can social behavior be divided into?

Most animals must maintain a balance between affiliation and aggression
affiliation: social behaviors that bring animals together
territorial/aggression: social behavior that keeps animals apart

• Affiliation is thought to evolve from what other behaviors? What hormone may be involved?

thought to have evolved from parental behavior.
Controlled by mechanisms co-opted from parental and reproductive bonding (conserved across species) but are distinct from those specific behaviors
Mainly depend on sex steroid hormones and peptide hormones (oxytocin and vasopressin)

• What are the overlapping brain regions controlling maternal love and romantic love?

Theory of affiliative behavior evolving from parental behavior is supported by fMRI showing some overlapping areas of activation (orange) for people viewing photos of their babies and photos of romantic partners

Areas such as: putamen, caudate
nucleus, and medial insular and
interior cingulate cortices

What is interesting about these regions in relation to attachment?

As well as involving a lot of the same hormones, a lot of the same brain regions are activated by both romantic and maternal love.
And interestingly, two of those areas (the 1st 2) are part of the major reward pathway of the brain.
And the other two areas they had in common have high densities of AVP and OT receptors.

What is the basis of pair-bonding differences?

testosterone
oxytocin
vasopressin

What is different about OTR in monogamous vs polygamous voles? Why do you see a difference?

The prairie voles have more OTR in the nucleus accumbens, fronto-parietal cortex, lateral amygdala, and the thalamus.
The Montane voles had more OTR in the lateral septum
Vassopressin is also involved
why? they display different social strategies.
prairie voles are monogomous and tolerant of other voles while montane voles are polygamous and not tolerant.

• What is the role of Dopamine in pair-bond formation?

Also key areas in the mesolimbic dopamine reward system
Injection of Da agonist promotes bond formation in females while Da antagonist blocks pair bond formation
This suggests that pair-bond formation uses the same neural circuitry as reward to make pair-bonding feel rewarding

Reward processing depends on the mesocorticolimbic dopaminergic system consisting of dopamine neurons in the ventral tegmental area and their projections to the nucleus accumbens, prefrontal cortex and other brain areas27. The ventral pallidum is a major target of the nucleus accumbens28, 29, and it further processes and relays stimuli from the nucleus accumbens to mediate locomotor responses to rewarding stimuli

**3. Vasopressin:

Different AVP receptor distribution between monogamous and polygamous voles too
Higher number of V1aRs (AVP receptor) in key areas: ventral pallidum, medial amygdala, mediodorsal thalamus of Prairie voles

what two things work together to promote pair-bonding?

prairie voles have higher expression levels of __________

As we saw on the previous slide, AVP and Da act together to promote pair-bonding in monogamous species like prairie voles.

Prairie voles have have higher expression levels of the V1aR in the ventral pallidum compared to polygamous meadow voles.

Where a receptor is expressed changes what kind of behavior it influences

• What is the three-chamber preference test? What type of results do you see with this test? What happens when you increase AVP receptor expression in polygamous voles and test in the three-chamber preference test?

Lim et al., 2004

Used a viral vector to introduce DNA into cells in
the ventral pallidum (VP) specifically,
which lead to overexpression of the V1aR
in this area in male Meadow voles

Resulted in 3-fold more V1aR binding in
the VP compared to controls (control virus
and off-target injections)

V1aR overexpression in wrong area

Test: Partner preference test
In a 3-chamber apparatus the freely-moving subject can choose to spend time with a female it has been housed with for 24 hours, or a novel female. Both females and tethered in their respective chambers.

Measure: Huddling time (significant preference indicates a pair-bond has formed)

Results 1: Increased expression of this single gene for V1aR in the VP resulted in normally polygamous voles that do not show social bonds to now display significant preference for huddling with partner over stranger. This
indicates that a pair-bond was formed due to increased AVP binding in VP.

Results 2: Administration of a Dopamine D2- receptor antagonist prior to the 24 hours of housing with partner prevented this pair-bond from forming in the V1aR-overexpressing Meadow voles. Indicates that Da transmission is necessary for pair-bonding to be rewarding and for forming conditioned partner preference.

• Are high levels of testosterone expected in polygamous or monogamous species? What is the benefit of having low levels of testosterone?

Males from monogamous species have lower testosterone concentrations and smaller testes than those of polygamous species
Prairie voles have about half the plasma testosterone concentration of meadow voles
However, experimentally increasing or decreasing testosterone in male voles does not cause them to switch mating strategies, so not causally sufficient.

benefit of having low testosterone: inhibits aggression, tolerant of other voles

Affiliation Summary:

Affiliative behaviors were evolutionarily co-opted from parental behaviors and depend on similar hormones

Hormones can control the type of social bonds species form and their mating systems, namely: Testosterone, Oxytocin, and Vasopressin

For monogamous species, OT and AVP activity in structures of the mesolimbic reward pathway serves to make pair-bonding rewarding

• What is the definition of aggression (Moyer, 1968)?

Aggressive behaviors keep animals apart; involves overt behavior with the intention of causing harm or other unpleasantness to another individual
Is partially mediated by some of the same circuits as affiliation, but not entirely

What are some types of aggression?

Different types of aggression appear in different contexts and have different physiological causes
Types of Aggressive Behavior:
Predatory
Fear-induced
Territorial
Maternal
Intermale
Social conflict
Irritable

Most natural occurrences of aggressive behavior take place because of competition over limited resources

• What circumstantial evidence links androgen levels to aggression?

Circumstantial evidence that androgenic steroid hormones mediate aggression:
1. Seasonal variations in blood plasma concentrations of Testosterone coincide with seasonal rises in aggression
2. Aggressive behaviors increase at puberty when blood concentrations of androgens rise
3. Across nearly all species, males are generally more aggressive than females
4. Preventing androgen production (i.e. castration) typically reduces aggression in males, but this can be reversed using testosterone replacement

There is overwhelming circumstantial evidence that androgenic steroid hormones mediate aggression.
A lot of these points we will explore in greater detail

• Why do male red deer display aggressive behavior during the fall?

Intermale aggression and growth of antlers in red deer is dependent upon a large increase in testosterone production leading up to annual mating season.
Throughout the year, males live together
with little aggression, but when mating
season approaches, they fight for territory
which gives them access to mates.

What is the correlation between testosterone, antler growth, and aggression in red deer?

At the end of the summer, T levels increase and peak in mid autumn, the rising androgen levels are accompanied by antler growth, and aggressive behavior. Mating occurs for about 2 weeks in mid autumn. After mating, T levels diminish, aggressive behaviors wane, antler growth ceases, and males engage in few agonistic interactions.

What are the effects of castration in red deer?

Fighting helps to establish the social rank of male deer. Higher status results in higher access to mates.
Fighting ability depends on antlers
Normally, antlers are shed in the late winter after mating season has ended and T levels drop
Castration of male deer halts testosterone production and results in early shedding of antlers and a plummet
in social status
Removal of antlers in gonadally-intact males still results in loss of status

So from these results you can gather that testosterone levels are playing a large role in the aggression and social behavior of the deer and that the timing of it is important. Having more T when other males have low T is an advantage. Having lower T than the other males is a disadvantage.

The effects of testosterone implantation in summer and winter?

Castrated males given slow-releasing capsules of T during winter were more aggressive, retained their antlers, and rose in social rank while the T of other males was dropping.
Castrated males given T in the summer were still more aggressive even without their antlers growing back yet and rose in social status as a consequence

Demonstrates that T affects social status of males in 2 ways:
1. by acting directly in the brain to promote aggression
2. by acting on antlers to provide 'weapons' to inflict aggression

• What allows group living in winter in rodents and why is it beneficial? What hormone mediates this?

Rodent species (e.g., meadow voles) that are more aggressive during breeding season and warmer weather become more tolerant of other rodents in winter to increase survival
- conserve energy
- share warmth by huddling

This decrease in aggression is accompanied by lower androgen concentrations, decreased number of androgen receptors, and reproductive regression

In some species, castrated males still exhibit seasonal aggression
(e.g. wood rats and prairie voles)

In other species like Syrian and Siberian hamsters, decreased androgen levels due to winter-like conditions results in an increase in aggressive behavior

This means Androgens are not mediating aggression here
What could account for this?

• What is another possible mediator of aggression in some rodent species? How does this mediator change effects based on season?

Explanation: An estrogen signaling system that also mediates aggression seasonally
Example: in male oldfield mice, in summer conditions, estrogens inhibit aggression but in winter-like conditions estradiol injection increases aggression

Rapid effects of injection in winter are mediated by nongenomic mechanisms (phosphorylation of kinases & regulation of transmitter release)

Inhibitory effect of estradiol injection on aggression in summer conditions is mediated by changes in gene expression (slower)

• In what season do we expect humans to behave more aggressively?

Human males show seasonal variation in blood testosterone concentration, but a direct causal link to increased aggression has not been established
Circumstantial evidence:
- Peak violent crime rates in North America are associated with high temperatures and peak androgen concentrations
- Survey of women abused by live-in male partners reported an annual rhythm of abuse, with summer being the peak
- Increased violations in prison population in summer
> Still are just correlations

• What causes increased levels of circulating androgens in males during puberty?

The testes grow larger
They secrete increasing amounts of androgens
Rise in circulating androgens is correlated with increased aggression
This is true across many species, including humans

Aggression & Puberty
syrian hamsters

In Syrian hamsters, fighting style follows a defined pattern across development
Normally, as age increases, fighting frequency decreases
Impact of social stress:
- Exposure to aggressive adults hastens this transition into adult fighting style
- Repeated social stress slows the decline in attack frequency
- Mediated by HPA axis maturation
- Not impacted by castration

• What are the different areas hamsters focus on when they attack other con-specifics and how does this focus change during puberty?

Prepuberty: attacks aimed at face- mostly play fighting
mid-puberty: attacks aimed at flanks
Post puberty: adult fighting style of attacking underbelly and rear of opponent
Being exposed to aggressive males increases plasma cortisol levels. This increase in cortisol is normally a marker of fighting style maturation, this is why it makes the change happen sooner.
Castration of pre-pubertal males does not prevent this transition from play-fighting to adult fighting

• Why do male rodents show enhanced aggressive behavior during puberty? What is the evolutionary advantage of this behavior?

What is the benefit of aggression peaking around puberty far male rodents?
This is a dangerous time for males because it coincides with dispersal (leaving home)
Dispersal exposes them to new threats like:
Infringing on territory of other males
Competing for food
Competing for mates
Exposure to predators

There is evolutionary value in increased aggression
at this time

The higher the population density, the more aggression males are exposed to, and in turn, the more aggressive they become, like in the case of the socially stressed syrian hamsters

• What are the two strategies primates use to join a new group during the pubertal period and what hormones are associated with each of these strategies?

Dispersal also occurs in primates during puberty. For example, young male rhesus monkeys become the target of adult aggressive behaviors in their natal group at this time, and must find a new group to join
There are 2 general strategies for joining a new group:
1. Burst in and seize membership status
2. Wait in the periphery and sneak in

Behavioral and endocrine factors predict what strategy a monkey will use:
Young males from high-ranking moms exhibit more risk-taking behaviors, have lower autonomic reactivity, and lower plasma cortisol concentrations > they choose burst in
Young males of low-ranking mothers have high autonomic reactivity and high blood cortisol levels (suggests more stress exposure) > they choose sneak in

• What were the 3 major theories discussed that help to explain sex differences in aggression in boys and girls?

1. Males have higher concentrations of circulating androgens
2. Males are exposed to androgens prenatally, which causes organization of brain in a way that facilitates aggression
3. Social influence: boys are encouraged, girls discouraged

• Understand how we know that aggression is organized perinatally by androgens but requires the presence of androgens after puberty to be fully expressed.

male mice castrated before day 6 + T in adulthood = low levels of aggression
females OVX before day 6 + androgens in a adulthood = little to no aggression
gonadoectomized males or females before day 6 + T before day 6 and in adulthood = both sexes show normal aggression levels seen in typical males

What does this tell us?
Aggression in male mice is both organized and activated by androgens

- In other words, males normally act more aggressive than females due to perinatal organization by androgens, but also that androgens must be present after puberty for the behavior to be expressed

• In which species are females more aggressive than males?

Female Syrian Hamsters are usually more aggressive than males. Housing condition does not significantly affect aggression level in intact hamsters.

Estradiol and progesterone are acting like testosterone

• How can behavior affect hormone concentrations? What hormones are affected? What are some examples of how this happens?

Competition in Animals:
In several species, male androgen levels decrease after losing a fight
This suppression can last for days-weeks after defeat
Winning males have increase in T after fight

• Describe the winner effect seen in California mice.

In male California mice, winning fight enhances ability to win and motivation to engage in subsequent fights, but only if previous win was in its home cage.

This effect is mediated by androgens via up-regulation of androgen receptors in reward processing brains areas (e.g., VTA and nucleus accumbens)

• Understand how hormones are affected in human competition.

Competition in Humans:
Perceived rivalry with other soccer team increases T
levels in players before game
T levels increase more in players about to compete with
a more challenging team
Players on home field have higher T

Males students played a doubles tennis match, best of 5 wins $200. Measured testosterone 1 hour before and after the game
-Doubles that won had elevated T relative to losers
-Doubles that just barely won and had a close match had no difference in T compared to losers
Males paired and given a 50/50 chance of winning a $100 prize based on lottery. Took T levels before and after
-Winning prize did not affect T in this competition

> Blood T levels are more likely to be affected by winning a contest if the outcome is due to the man's effort.

• What is conditioned social defeat?

A Syrian hamster defeated in its home cage will subsequently fail to defend their own home cage, even if the new intruder is smaller or non-aggressive
Defeat evokes a stress response (like fear conditioning): elevated HPA activity, ACTH, cortisol, and decreased T and prolactin in response to exposure to another male
Can last at least 33 days and possibly through adulthood
Female hamsters do not really exhibit conditioned defeat; some display low levels of submissive or defensive behaviors, but only for short time

• What are the two main theories for the effects of androgens on human antisocial behaviors?

There is a positive correlation between circulating blood androgen concentrations and violence in people incarcerated for violent crimes

Affect of androgens on human antisocial behavior: 2 hypotheses
Direct effect: Androgens directly mediate anti-social behaviors by directly acting on brain areas that mediate aggression

Indirect effect: Androgens promote a constellation of traits including social dominance, competitiveness, and thrill seeking that can be expressed as either anti-social or prosocial behavior depending on the individual's resources and background (AKA environment as a moderator)

Key Aggression Circuit Ares:

Prefrontal cortex
Amygdala
MPOA
Hypothalamus
Anterior cingulate cortex
Insular cortex
Ventral striatum
These are the brain regions that have been implicated in aggressive behavior in rodents and non human primates. Functional or structural abnormalities in any of these regions can increase the susceptibility for impulsive aggression and violence.

• What is the aggression circuit in rodents?

A) in rodents information from the OB is processed by the medial amygdala and sent to the lateral septum (LAS), Bed Nucleus of the Stria terminalis, and the anterior hypothalamic area (AHA). It ultimately ends in the PAG which promotes species specific aggression. Stress can inhibit aggression via inhibitory inputs from the OFC (orbitofrontal), hippocampus and PVN (paraventricular nuc).

what is the aggression circuit in primates?

B) in primates, aggression is evoked by visual or vocal signals. Activation of the MEA results in activation of BNST and anterior hypothalamus (AHA) which activate PAG for aggressive output. Inputs from OFC might inhibit aggression by reducing MeA responsiveness.

What is a common structure in both that mediates aggression?

the PAG mediates aggression for both

**Physiological Mechanisms- Rats
fmri

fMRI study of male rats exposed to a male intruder and a female cage mate during scan
Exposure to other male + mate= increased activation in medial basal amygdala and lateral hypothalamus (aggression circuit areas)

Decreasing Aggressive response:
Treatment with an SSRI suppressed this activation

Treatment with Vasopressin Va1 receptor antagonist also suppressed this activation

• How does 5HT affect aggression?

Nearly all neurotransmitters have been implicated in some way in aggressive behavior, of these, serotonin (5-HT) is considered the most influential regulator of aggression
Two 5-HT receptors that influence aggressive behavior: 5-HT1A and 5-HT1B
Low 5-HT function or low receptor activation is associated with higher aggression
> So high 5-HT function/receptor activation = low aggression
Testosterone and estradiol may support aggressive behavior by acting on
5-HT function
example: androgens and estrogens modulate 5-HT1A and 5-HT1B receptor function during aggressive acts

Social Behavior Summary

Oxytocin and Vasopressin are associated with affiliate behaviors and work in combination with Dopamine to promote affiliation in monogamous species
Androgens and estrogens help to mediate aggressive behavior, often depending on an advantageous seasonal rhythm
Puberty is a time of increased androgen production in males, often leading to a spike in aggressive behaviors
Social experience can feed back to influence hormone production based on the outcome of interactions
Functional or structural irregularities in aggression circuit areas can increase the susceptibility for impulsive aggression and violence

• What is homeostasis?

The process by which animals maintain a fairly stable internal environment

Be able to describe the analogy of a thermostat as a homeostatic device.

Most homeostatic systems operate like a thermostatically controlled heating and cooling system
-Thermostat (Sensor) acts to keep the room temp within a narrow range around the set point
-When the temp falls below the set point, furnace is activated to raise temp
-When the temp rises above set points, the air conditioner is engaged to reduce temp
-Once temp returns to set point furnace or air conditioner shuts down
The deviation from set point must be a few degrees otherwise the system would be continuously engaging and turning off with only minor changes in temp ("set zone")

• How do endotherms regulate temperature?

Most mammals and birds
Maintain an internal body temp within a narrow range around 37o C (36-38oC or 97-100oF) because this is the optimal temp for most bodily reactions
Temps too low or too high can seriously endanger the individual
Regulate body temp chiefly by internal processes but also use behavioral methods

How do ectotherms regulate temperature?

Not by physiological methods
Instead, body temp is regulated by the environment and behavioral methods

• How does body temp change when we are ill and why? How do iguanas regulate their body temp when they are ill? What is the adaptive consequence?

In the laboratory, iguanas will regulate their body temp by moving toward or away from a heat source and settle where it can maintain its body temp at 37o C

If an iguana is infected with a bacteria they will behaviorally produce a fever to fight the infection by positioning themselves closer to the heat

This has adaptive consequences because a greater percentage of iguanas survive if they able to elevate their temperature

• What are thermoreceptors? Where are they found?

detect blood temperature
found in the anterior hypothalamus

there are also thermoreceptors in the skin that detect external temperature

• What area of the brain controls thermoregulation?

the hypothalamus controls thermoregulation

What input does it (the hypothalamus) receive?

central (anterior hypothalamus) and peripheral input.
the central input includes the thermoreceptors in the hypothalamus
the peripheral input includes thermoreceptors in the skin

What effectors do they regulate?

The thermoregulatory center of the hypothalamus regulates the following effectors:
smooth muscles in arterioles, sweat glands, erector pili muscles in skin, skeletal muscles, and adrenal and thyroid glands.

Be able to describe the various responses to high and low temps.

PHYSIOLOGICAL AND BEHAVIORAL RESPONSES to adjust body temp:
smooth muscles --> vasodilation and constriction
sweat glands --> sweat
erector pili --> skin hairs stand up
skeletal muscles --> shivering
adrenal and thyroid glands --> metabolic rate

Be able to describe the various responses to high and low temps.
in more detail:
effector: smooth muscles in peripheral arterioles in the skin:

low temperatures: muscles contract using vasoconstriction. less heat is carried from the core to the surface of the body, maintaining core temperature. extremities can turn blue and feel cold and can even be damaged (frostbite)
high temp: muscles relax causing vasodilation. more heat carried from the core to the surface, where it is lost by radiation. skin turns red.

Be able to describe the various responses to high and low temps.
in more detail:
effector: sweat glands

low temp: no sweat produced
high temp: glands secrete sweat onto surface of skin where it evaporates. water has a high latent heat of evaporation so it takes heat from the body

Be able to describe the various responses to high and low temps.
in more detail:
effector: erector pili muscles in skin (attached to skin hairs)

low temp: muscles contract, raising skin hairs and trapping an insulating layer of still, warm air next to the skin. now very effective in humans, just causing goosebumps
high temp: muscles relax, lowering the skin hairs and allowing air to circulate over the skin, encouraging convection and evaporation

Be able to describe the various responses to high and low temps.
in more detail:
effector: skeletal muscles

low temp: muscles contract and relax repeatedly generating heat by friction and from metabolic reactions
high temp: no shivering

Be able to describe the various responses to high and low temps.
in more detail:
effector: adrenal and thyroid glands

low temp: glands secrete adrenaline and thyroxine respectively, which increase the metabolic rate in different tissues, especially the liver, so generating heat.
high temp: glands stop releasing adrenaline and thyroxine

Be able to describe the various responses to high and low temps.
in more detail:
effector: behavior

low temp: curling up, huddling finding shelter, putting on more clothes
high temp: stretching out, finding shade, swimming, removing clothes

• What are the two types of thirst and what are they caused by?

Osmotic thirst: If the concentration of NaCl in the extracellular fluid increases osmosis will draw water out of the cells --> cellular dehydration --> potent stimulus for osmotic thirst
Induced by consumption of salty or sugary foods

Hypovolemic thirst: Caused by reduced blood volume as a result of hemorrhage or excessive diarrhea, vomiting, perspiration

How are they (the two types of thirst) detected (know the types of receptors and where they are found)?

Osmotic:
Cellular dehydration detected by osmoreceptors
Found in circumventricular organs -areas of the brain where the blood brain barrier is weak
Osmoreceptors thus have access to peripheral blood to monitor solute content in blood

Hypovolemic:
Drop in blood volume and pressure is detected by baroreceptors (stretch receptors located in the major blood vessels and heart)

What hormone(s) does each type of thirst stimulate the secretion of and what effects do they have?

osmotic:
Cellular dehydration detected by osmoreceptors causes vasopressin (antidiuretic hormone, ADH) secretion from the posterior pituitary -->
1. Promotes water conservation by the kidneys (i.e. decreased urine output)
2. Stimulates drinking behavior

Hypovolemic:
Drop in blood volume and pressure is detected by baroreceptors (stretch receptors located in the major blood vessels and heart) --> ADH release from posterior pituitary -->
1. vasoconstrictor --> increase blood pressure
2. water conservation by kidneys
Cardiac baroreceptors also signal the brain directly via the vagus nerve to stimulate thirst
Hypovolemia also stimulates the release of the enzyme renin from the kidneys which converts angiotensinogen --> angiotensin II which has several water conserving actions
Aldosterone: mineralocorticoid steroid hormone released from adrenal glands which stimulates kidneys to conserve Na⁺ --> water reabsorbed from blood --> water retention

What quenches each type of thirst?

Drinking water quenches osmotic thirst

Drinking water will NOT quench hypovolemic thirst! Must replace water, as well as sodium, and other solutes. (gatorade)

• What is diabetes insipidus? What are its causes, symptoms and treatment? What animal model mimics this disorder?

ADH important for fluid balance
Deficiency in ADH secretion due to pituitary damage from head trauma, infections or tumors, genetic disorder
Major symptom: excessive fluid intake and urine productions (up to 16L per day!)
Treated with exogenous ADH (desmopressin)
Battleboro rats: congenitally lack ADH as a result of a genetic mutation

• What hormone maintains physiological homeostasis of sodium balance? How?

Because Na+ is a major component of extracellular fluid and is important for fluid balance, it too must be maintained at a within precise limits (135-145 mmol/L in blood plasma)
Under normal conditions, physiological homeostasis maintains Na+ balance through aldosterone from the adrenals which acts on kidneys to conserve Na+
When physiological homeostasis fails, behavioral homeostatic processes are engaged to sustain life

• What happens to a rat if the adrenal glands are removed? Why? What can prevent this? What is salt intake like before and after adrenalectomy? How is this an example of behavioral homeostasis?

Adrenalectomized (ADX) rats usually die within one week because without aldosterone, they cannot retain enough sodium
Before ADX the animal drinks very little salt but afterwards salt intake increases dramatically and the rat will survive as well as intact rats
If given salty water soultion then they can replace the salt lost , intact rats do not like salty water , but ADX rats will display behavioral homeostasis to surivive, they start preferring salty solutions at high levels

How is this different in Syrian hamsters? Does this prove that hamsters are less intelligent than rats? Why or why not?

Like rats, Syrian hamsters will perish if ADX
However, ADX hamsters provided with salt water will refuse to drink it and die
Will drink salt if it is mixed with saccharine and they will live
If given a choice: NaCl or saccharine? Then, the hamster drinks saccharine and dies
Does this prove that hamsters are less intelligent than rats?
-Not necessarily
-Hamsters evolved in the desert where sodium is high and water is scarce
-Finding sodium not a physiological problem
-Have adopted behavioral and physiological strategies to avoid sodium!

• Are herbivores adapted to retain or excrete sodium? Why?

Obtain sodium from plants
There is a range of sodium content in plants so they may be exposed to a wide variation in sodium availability
Adapted to retain sodium

Are carnivores adapted to retain or excrete sodium? Why?

Not under the same sodium pressures as herbivores
The animals carnivores eat must maintain their own sodium balance
Adapted to excrete sodium

• What did the Blair West et al. (1968) study demonstrate?

Demonstrated that animals can cope with a variations in sodium availability in their environment by adapting their physiology, morphology and behavior to maintain sodium homeostasis
Studied a population of European rabbits that were brought to Australia
These rabbits ranged over several types of habitats with varying levels of sodium availability
-Some inhabited the snowy mountains (where the vegetation is naturally low in sodium)
-Others lived in desert or seashore (where the plants have high levels of salt)

Be able to describe the differences between snowy mountain rabbits and desert rabbits.

Snowy Mountain Rabbits (low sodium)
Hypertrophied zona glomerulosa of the adrenal cortex (produces aldosterone)
High blood aldosterone (conserves salt) concentrations
Urinary sodium content was very low-undetectable
Voracious sodium appetite (devoured salt from salt licks provided by experimenters)

Desert Rabbits (high sodium)
Narrow zona glomerulosa of the adrenal cortex
Low blood aldosterone
High urinary concentrations of sodium
No salt appetite (don't ingest salt from salt licks provided by experimenters)

• What are the two phases of energy utilization and storage after a meal? What occurs during each? What hormone promotes energy storage? How?

After eating a meal, there are two phases of energy utilization and storage :

1. Postprandial
occurs immediately after ingestion
a supply of metabolic fuels in the forms of glucose, fatty acids and amino acids enter the blood stream
Unless you are running a marathon after eating, there will be surplus energy

2. Postabsorptive
excess energy is stored
Insulin`

• In a fasting state, what hormone promotes the release of stored energy? How?

glucagon

Eventually, blood concentrations of glucose drop and the body must shift from putting energy into storage into getting it out of storage

• What endocrine gland releases the hormones involved in energy storage and release? Know the specific cell types.

pancreas

insulin:
ONLY hormone responsible for energy storage
Released from pancreas by beta cells
Acts to promote uptake of glucose into tissues for oxidation (i.e. brain, muscles) and storage (i.e. liver, muscle, adipose) in the form of glycogen through the process of glycogenesis
In doing so insulin lowers blood glucose levels

Glucagon
Released from pancreas by alpha cells
Induces glycogenolysis
-breakdown of stored glycogen into glucose by liver
Also induces lipolysis in adipose tissue which releases free fatty acids (FFA)
-In the liver, FFA ketone bodies and glucose
Amino acids in the liver can also be converted to glucose
(gluconeogeneis)

Glucose and ketone bodies power the brain
Ketone bodies and FFA fuel muscles

• Know the different causes of type I diabetes as well as the population most affected and treatments.

Type I
Insulin dependent mellitus
Autoimmune disorder in which the b cells of the pancreas are destroyed by the immune system resulting in an insulin deficiency
Rapid onset, most common in children and young adults
Treatment involves replacement of missing insulin via injection

• Know the different causes type II diabetes as well as the population most affected and treatments.

Type II
Tissues develop an insensitivity to insulin
Develops slowly in adults over the age of 40, associated with obesity
Incidence is rising among younger obese individuals
Early stages can be controlled by diet and insulin treatment isn't required but if left uncontrolled, can cause the pancreas to stop producing insulin requiring the use of exogenous insulin treatment

What is the main consequence of both types? What are the symptoms?

Individuals with either type of diabetes have trouble moving surplus glucose out of the blood resulting in symptoms which include:
elevated appetite (body can't make efficient use of digested food)
increased thirst and urination (in an attempt to rid body of excess glucose)
high blood glucose (hyperglycemia) which can be toxic and lead to other health problems including neuropathy, poor circulation and blindness

• What is the "dual-center" hypothesis? Is it accurate?

For many years "Dual-center" hypothesis though to be correct
-This model proposed two appetite centers-one to signal hunger the other to signal satiety
-Hunger center in Lateral hypothalamus (LH): LH-lesioned animals displayed aphagia (refusal to eat) and weight loss
-Satiety center in ventromedial hypothalamus (VMH): VMH lesioned animals displayed hyperphagia (excess feeding) and weight gain
-Appetite balancing act between hunger and satiety centers

This hypothesis proved to be too simple to account for the regulation of feeding

• What hormone that we discussed in class acts as an adiposity signal? In what brain region are receptors for this hormone found?

leptin acts as an adiposity signal
receptors for leptin are found in the arcuate nucleus

In the arcuate nucleus region, what are the two signaling molecules produced by the feeding stimulatory circuit?

Feeding Stimulatory Circuit (Anabolic) produces two orexigenic peptides that stimulate food intake, reduce metabolism and promote weight gain:
NPY (neuropeptide Y)
AgRP (agouti related protein)

In the arcuate nucleus region, what are the two signaling molecules produced by the feeding inhibitory circuit?

Feeding Inhibitory Circuit (Catabolic) produces two signaling molecules that inhibit food intake, increases metabolism and promotes weight loss:
POMC produces a-MSH
CART (cocaine- and amphetamine-regulated transcript)

Where do these (feeding inhibitory and stimulatory) circuits project?

Both circuits:
Are modulated by peripheral signals that cross or are transported across the BBB

send signals to PVN and LH which then directly modulate feeding behaviors

NPY/AgRP circuit projects into the PVN
POMC/CART circuit projects into the LHA/PFA

What effect do high levels of leptin have on the stimulatory pathway and inhibitory pathway? What effect do low levels of this hormone have on the stimulatory pathway and inhibitory pathway?

High leptin (high energy reserves) decreases feeding behavior by inhibiting NPY/AgRP neurons and stimulating POMC/CART neurons
-Inhibit feeding 'on' circuit (NPY)
activate feeding 'off' circuit (POMC)

What happens when leptin levels are low (low energy reverses)?
-Feeding 'on' circuit activated; feeding 'off' circuit inhibited

• What effect does ghrelin have on feeding? How?

Ghrelin acts to stimulate feeding by activating AGRP/NPY neurons

• What role does the nucleus of the solitary tract (NTS) play in hunger and satiety? What effect does cholecystokinin (CCK) have on food intake?

NTS (nucleus of the solitary tract) in brainstem receives and integrates appetite signals from a variety of sources in addition to the hypothalamus including:
1. Liver: detects glucose and communicates this info to the NTS via the vagus nerve
2. Gut: peptides like CCK (cholecystokinin) which reach the NTS through the vagus nerve and sympathetic fibers

both anabolic and catabolic pathways feed into the NTS.

Together these signals regulate food intake

CCK decreases food intake (satiety signal)

• Why do humans have a tendency to accumulate excess energy?

Like it or not, our evolutionary history has optimized our bodies for obtaining and storing energy to enhance survival in environments where energy availability fluctuates
Protecting against accumulating too much energy was not a concern for our distant relatives
The tendency to accumulate excess energy is exacerbated by our sedentary lifestyles

What are some approaches being investigated to treat obesity or that are being used currently?

-Increased metabolism: thyroid hormones (unwanted side effects i.e. high rate unless can activate TH-R associated with metabolism without affecting TH-R associated with cardiovascular function)
-Inhibition of fat tissue formation: angiogenesis inhibitors
-Reduced absorption: Xenical interferes with digestion of fat (only modest weight loss, intestinal discomfort)
-Reduced reward
-Gut bacteria: "microbiome"
-Appetite control: cannabinoid antagonists ("anti-munchies"), leptin

Can leptin be used to treat obesity? Why or why not?

Many obese people have abnormally HIGH levels of leptin because lots of adipose tissue.
Leptin resistance (like insulin resistance)
The body is constantly in 'starvation' mode hormonally --> EAT!
No amount of leptin will lead to satiety IF BRAIN IS RESISTANT. Need to decrease leptin resistance instead

Which, if any, are effective?

Anti-obesity surgery :
-Liposuction:
--surgical removal of fat
--only moderately successful and temporary
--Fat usually regrows after excision
-Bariatric Surgery:
1. Gastric bypass: Sleeve lines small intestine to reduce calorie absorption
2. Gastric banding: band placed around the upper part of stomach to create a small pouch to hold food, limits the amount of food that can be eaten (i.e. feel full after eating small amounts of food)
-Although doesn't directly target appetite controlling mechanisms, changes in appetite hormones accompany surgery
-Produces a significant and lasting weight loss
-Accompanied by significant complications and risks

• What are the key components of biological rhythms? Over what time scale(s) do biological rhythms vary?

Biological rhythms are characterized by:
Period: Length of time before rhythm repeats itself
Frequency: How often the rhythm recurs
Amplitude: The size of the variability in the biological outcome
Phase: The point of the cycle being measured

Period of biological rhythms range from ms to years

Different lengths of biological rhythms can occur in same measure

• What are isolations experiments? What do they determine?

isolation experiments determine whether a rhythm is the result of exogenous or endogenous factors

If remove environmental cues and the biological rhythm:
Persists --> rhythm is Endogenous/generated within animal
Disappears --> rhythm is Exogenous/driven by environmental cue

Be able to describe the experiment and findings of Jean Jacques d'Ortous de Mairan and why they were important.

De Marian's experiment (1729) - Tension-relaxation pattern of heliotropic plants (move in response to sun)

- Persist even if plants isolated from exogenous factors (i.e. sun)

- Rhythm is ENDOGENOUS

• What are 3 types of evidence that biological clocks are endogenous and not driven by the environment?

Animals maintained in space (away from tides, light/dark cues, etc...) maintain biological rhythms similar to those observed on earth

Animals maintained in adjacent, but individual, cages in the absence of environmental cues display biological rhythms with slightly different periods suggesting that are not being driven by the same geophysical cues

Period and phase of biological rhythm of one individual can be 'transferred' to another by means of a tissue transplant (master biological clock)

• What is a free running rhythm? What does it represent? What is entrainment? What is a zeitgeber?

Entrainment: process of synchronizing a an endogenous biological rhythm to an environmental cue (zeitgeber or "time-giver")

These rhythms persist when animals are isolated from their environmental cues but only approximately (free running rhythms)
Free-running rhythm that represents the endogenous rhythm

• What are 4 types of biological rhythms that are synchronized with ENVIRONMENTAL cues? What are their entrained period lengths (i.e. when environmental cues are present)? What are their free-running period lengths (i.e. when animals are isolated from their respective environmental cues)?

circadian: revolution of the earth (environmental cycle), 24 hours entrained, 22-26 hours free-running
circatidal: tides (env cycle), 12.4 hours entrained, 11-14 hours free-running
circalunar: phases of moon (env cycle), 29.5 days entrained, 26-32 days free-running
circannual: seasons of the year (env cycle), 365.25 days entrained, 330-400 days free-running

• What is an important experimental technique used in the study of circadian rhythms in small mammals like hamsters?

locomotion
Wheel running and actograms which show activity patterns plotted across the days over multiple days

Newer set-ups use live-tracking to image when and where animals are active

• What is an important environmental time cue for hamsters and most other species?

Zeitgeber: light

• If a hamster is housed in conditions where lights are off for 12 hours, then on for 12 hours, when will the hamster run? What happens if the environmental light-dark cycles are phase shifted (e.g. lights are turned off 4 hours later)? If the hamster is housed in constant dim light, what happens? What does this tell us about circadian rhythms?

When housed in a light/dark cycle, animal becomes active during night
-Entrained rhythm
If the onset of darkness is shifted by 4 hr*, then the animal will adjust to the new cycle
-Phase shift: shifts activity in response to the synchronizing stimulus of light
-Similar to jet lag when humans travel to different time zones and daylight savings time
If the animal then placed in constant dim light, it will become active a few minutes later each day but continues to show rhythm
Free-running rhythm > 24 hr represents endogenous rhythm

Circadian rhythms are endogenous (self-sustained) but they are adjusted or entrained to the environment by external cues called zeitgebers, the primary one of which is daylight.

• What happens to the sleep wake cycle of humans placed in a dark cave with no external cues? What does this suggest?

Human subjects were placed voluntarily in a dark cave with all cues to external stimuli removed
Before isolation on day 5: normal sleep wake patterns.
After isolation: onset of sleep a little later every day which caused the rhythm to shift from 24 hr --> 25 hr
Humans have an endogenous clock
External cues typically entrain our clock to a 24 hr period and this circadian clock encourages the brain to sleep at some times of the days and to be awake at others.

example of endogenous circatidal rhythms

Locomotor activity pattern of fiddler crabs:
Move along beach during low tide, searching for food and mates
Return to burrows prior to onset of high tide

If moved to aquarium, will retain cycle of activity and become active at approx. same time as low tide (12.4 hr tidal cycle)

example of circalunar rhythms

Antlion hunts by building pit to catch prey
Increases activties during full moon
Even in constant conditions of lab will exhibit circalunar rhythm in average size of pits built, i.e. large pits when full moon

example of circannual rhythms.

Migratory patterns of birds

Even when kept in lab, birds show 10-12 month cycles of pre-migratory restlessness, weight gain and reproductive competence

• What are two types of biological rhythms that persist in constant conditions and do not correspond to any known geophysical cues? How often do they occur? Be able to provide examples of each.

Ultradian
Shorter than circadian, i.e. min-hours
Repeat more than once per day
Examples: 90 min cycle characteristic of REM sleep, appetite, arousal

Infradian
Longer than circadian , i.e. longer than a day but shorter than a month
Repeat less than one per day
Examples: ovarian cycles

• What is the usefulness of biological clocks?

Conductor of orchestra-makes sure everything timed appropriately
Synchronizing the activities of animals with their environments
- To prepare for predictable events (e.g., winter, night, etc.)
Synchronizing the internal physiological and biochemical processes of animals
To promote efficient functioning

Example: peak CORT occurs just prior to awakening --> increase blood pressure and cardiac output --> prepare you for onset of locomotor activity

Conductor of orchestra-makes sure everything timed appropriately

• What are the six general characteristics of biological clocks and rhythms?

Inherited
Temperature independent
Relatively resistant to the influence of chemicals
Entrained (synchronized) to only limited cycle lengths
Independent from behavioral feedback
Found at every level of organization within an organism

General characteristics of biological clocks - 1
Inherited

When mutant animals with free-running circadian rhythms > 25 hr are mated with one another, their offspring tend to have longer free-running periods than the offspring of mutants with free-running rhythms < 23 hr (and vice versa)

General characteristics of biological clocks - 2

Temperature independent

Activities or events that change body temp don't significantly alter circadian clocks

Otherwise there would be speed-ups and slowdowns and eventually all resemblance to a 24 hr period would be lost

General characteristics of biological clocks - 3
Relatively resistant to the influence of chemicals

If not, the food consumed would constantly be altering biological clocks

A few pharmacological manipulations have been shown, however, to affect clocks: Protein synthesis inhibitors, Alcohol (EtOH), Lithium, Heavy water (deuterium)

These interfere with processes like membrane permeability & protein synthesis needed for biological clocks to function

General characteristics of biological clocks - 4
Entrained (synchronized) to only limited cycle lengths

A circadian rhythm can be entrained to a 23 hr day by providing 11.5 hr of light and 11.5 hr of dark (same for 12.5 hr light/12.5 hr dark).

However, 10 hr light and 10 hr dark does not result in entrainment to a 20 hr day.

Instead, results in free-running with sporadic entrainment attained at irregular intervals.

General characteristics of biological clocks - 5
Independent from behavioral feedback

Suppose a hamster housed in DD is expressing a 24.25 h cycle of wheel running onset.
Hamster's wheel is locked for 10 days, then it is unlocked.
What time will the hamster begin to run?
2 possible predictions:
1. 15 min after last time - clock suspended time keeping while the rhythm of wheel running activity was not being expressed
2. 150 min after last time - clock continued to run even in the absence of behavioral feedback.

General characteristics of biological clocks -6
Found at every level of organization within an organism

Single-celled organisms (i.e. algae) possess circadian rhythms...machinery necessary to generate a rhythm must exist at the level of individual cells.

So, in multi-cellular organisms, does every cell possess its own biological clock?

Perhaps, but in multi-cellular organisms, it appears as if these individual biological clocks have been organized into some sort of hierarchical fashion with feedback imposed from above.

E.g., cells taken from hamster adrenals and maintained in culture will free-run at different rates. In the intact hamster, they free-run at the same rate.

• Where is the master circadian clock found in amphibians, fish, reptiles and birds? Mammals?

in amphibians, fish, reptiles, and birds, they have photoreceptors in the pineal gland.

Suprachiasmatic nucleus (SCN)
Mammalian master biological clock
Located above the optic chiasm in hypothalamus

Suprachiasmatic nucleus (SCN)

~10,000 cells per side
Individual cells of the SCN show precise changes in activity across circadian cycle
Since each SCN neuron produces its own daily rhythm, they must be networked together to produce synchronized rhythms of activity

In mammals, what is the evidence?
Evidence that the SCN is the Endogenous Clock

1) Greater activity in the SCN during the light phase (as measured using autoradiography for glucose usage)
2) SCN lesions abolish circadian rhythms
3) SCN maintains the circadian rhythm in the absence of inputs/outputs, i.e. it's intrinsic

4) SCN transplant studies using mutant tau hamster
-Has free-running cycle of 20 hr
-Transplant SCN from tau hamster into 24 hr hamster and turn it into a 20 hr hamster.
-Rhythm of the transplant recipient matches the rhythm of the donor so SCN is source of rhythm

• How does the master clock work?

Takes advantage of the time it takes to make and degrade proteins from mRNA

In humans, "larks" versus "night owls" have different versions of the clock gene

1. Two proteins, clock and cycle, bind together to form a dimer
2. the clock/cycle dimer binds to DNA, enhancing the transcription of the genes for other proteins, including per and tau
3. these proteins bind with one another and feed back to inhibit the effect of the clock/cycle dimer on their own transcription
4. these inhibitory proteins eventually break down, releasing the clock/cycle dimers from inhibition, allowing the cycle to start over again. the entire cycle of gene transcription, protein interaction, and protein degradation takes about 24 hours to complete
5. input from the retina can muddle the cycle.

• Be able to describe the major input and output pathways to and from the master clock in mammals.

light information goes from the eye to the SCN via the retinohypothalamic pathway.

The RHT consists of retinal ganglion cells that project to the SCN

Most of these retinal ganglion cells contain the photopigment
melanopsin

When the retinal ganglion cells of the RHT containing melanopsin detect light, they release glutamate in the SCN.

Glutamate leads to increased transcription of per gene entraining the molecular clock to the day-night cycle

Because biological rhythms are so pervasive, there are probably hundreds of SCN outputs.
Two important pathways:

1) PVN: regulates rhythms in most endocrine function

2) Pineal gland (indirect pathway): regulates sleep/wake rhythm

eye --> RHT --> SCN --> MFB --> RF --> SCG --> pineal gland

Neural circuitry to and from the SCN in mammals

Because biological rhythms are so pervasive, there are probably hundreds of SCN outputs.
Two important pathways:

1) PVN: regulates rhythms in most endocrine function
2) Pineal gland (indirect pathway): regulates sleep/wake rhythm

eye --> RHT --> SCN --> MFB --> RF --> SCG --> pineal gland

• How is the clock entrained by external cues?

Circadian rhythms entrain to light-dark cycles using different pathways, some outside of the eye

Amphibians and birds have photoreceptors in the brain and pineal gland
In mammals, light information goes from the eye to the SCN via the retinohypothalamic pathway

• Where is melatonin secreted from? When is it secreted? Is the duration of secretion important? What information does this provide an animal?

Pineal gland releases melatonin

Production inhibited by light coming in via RHT

Hormone of darkness because secreted almost exclusively at night (peaks at 4 am)

Melatonin tells the body it is dark and thus plays a role in sleep onset
Exogenous melatonin used to treat jet lag

The duration of secretion is important because when the days are long and the nights are short, there are less melatonin secretions,and when nights are longer there is more melatonin secretion. Seasonal species like hamsters can use this as a way to time seasonal cyles and their behaviors associated with those cycles. Syberian hamsters, when the days are short , they don't reproduce, their coat changes, don't mate, all by measuring melatonin secretions.

• What is photoperiodism?

Melatonin plays a role in photoperiodism:
Use of day length to time annual cycles and seasons
Duration of melatonin secretion varies with length of nights
Many species use this info to assess time of year and time reproductive physiology and behavior to seasons that favor reproductive success

• Describe the seasonal cycle of reproduction in hamsters. How can seasons be mimicked in the lab? What is the critical day length for reproduction?

In the fall: wild Siberian hamsters suppress their reproductive systems and develop winter coat for camoflage in the snow
In the lab, they will undergo identical changes (despite warm temps and abundant food) if the lights are on < 12.5 hr/day.

Keeping day length at 12.5 hr and maintain testis size

If day lengths held at short days in the lab (less than 12.5 hr), testes will regress

When day length reaches threshold, indicated by melatonin, abrupt change in reproductive status

How is the seasonal cycle of reproduction regulated?

In autumn --> short days (increased melatonin):
Causes hypothalamus to become more sensitive to negative feedback of gonadal steroids
Decreased GnRH and gonadotropin secretion
Gondal regression, hibernation
In spring --> long days (less melatonin)
Causes hypothalamus to become less sensitive to negative feedback of gonadal steroids
Increased GnRH and gonadotropin secretion
Gonds regrow, breeding

• What are some examples of non-reproductive seasonal changes?

In wild voles, brain weights and hippocampal mass higher in summer
In the lab, brain mass and hippocampal volume LD> SD
May be an energy saving adaptation or could underlie seasonal changes in spatial learning and memory (SD impaired)

What evidence exists showing the hormones directly impact aggressive behavior?

What evidence exists showing that hormones directly impact aggressive behavior? In controlled experiments, men who were randomly assigned to be castrated at birth show lower levels of aggression in adulthood than men who were not randomly assigned to be castrated.

Do hormones influence behavior?

Generally speaking, hormones change gene expression or cellular function, and affect behavior by increasing the likelihood that specific behaviors occur in the presence of precise stimuli. Hormones achieve this by affecting individuals' sensory systems, central integrators, and/or peripherial effectors.

How is most of the research investigating the causal impact of hormones on behavior conducted quizlet?

How is most of the research investigating the causal impact of hormones on behavior conducted? By performing experiments on non-human animals.

What is the scientific study of the interaction between hormones and behavior called answer choices?

This field of study is also called behavioral endocrinology, which is the scientific study of the interaction between hormones and behavior.