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1

Berthold’s Experiment

Transplanted testes developed blood connections and became functional (i.e. produced sperm )

Concluded that the testes produced a blood-born product that affects anatomy and behavior (since nerve connections severed)


1849: A. A. Berthold performed first formal endocrinology experiment
Demonstrated non-neural contribution by the testes required for normal development of a rooster

Prepubertal castration of male chick was used to make capons for more tender meat.
Berthold wanted to know if these extensive effects were dependent on neural connection to the testes.

• Transplanted testes were fully functional
• Birds with transplanted testes were entirely normal
– Normal appearance
• Combs, wattles, plumage
– Normal behavior
• Normal vocalizing
• Normal aggression
• Normal mating

• Hypothesized secretory product carried by blood to target tissues
– Learned later to be testosterone

2

Techniques in
Behavioral Endocrinology

Assays: measure hormone levels.
Bioassays
RIA, EIA, ELISA

Ablation and replacement

Lesion

Electrical stimulation

Optogenetics

Electrophysiological recording

Pharmacological Techniques: agonists & antagonists

Immunocytochemistry

Immediate early genes
Autoradiography

Western blot

In situ hybridization

Genetic manipulations

Histology

Brain Imaging

3

Endocrinology Technique #1:

Ablation & Replacement

This method is like that employed by Berthold.

It is the removal (ablation) of a suspected hormone source or by replacement via implantation or by injection of suspected hormonal chemicals

4

Technique #2:

Bioassays

The use of a biological response to determine the PRESENCE or AMOUNT of a particular substance in a sample.

Identifies the chemical processes in a hormone’s actions.

Involves testing the hormone on a living animal or cell culture.

Bioassays are often usefully conducted on alternate species from which a hormone has been derived.

Bioassay for Prolactin:
In this case, the cell height of the crop sac is going to differentiate dependent upon the amount of prolactin injected.

5

Technique #3: Immunoassays

The most famous form is the radioimmunoassay (RIA) and it is a technique that was first able to measure hormones PRECISELY.

Rosalyn Yalow received the Nobel Prize in for her work on this technique.

6

Radioimmunoassays

Type of Immunoassay.

1. Antibody to a Hormone and the Labeled Hormone are mixed in solution.

2. The Labeled Hormone binds with the Antibody.

3. Unlabeled Hormone is added.

4. The Unlabeled Hormone and Labeled Hormone compete for binding sites.

5. The percentage of bound Labeled Hormone is measured and a standard curve is developed.

6. The standard curve is used to determine the amount of Unlabeled Hormone in a given sample.

7

Technique #4: Immunocytochemistry

A technique that it uses antibodies to determine the LOCATION of hormones or hormones receptors.

Often, these antibodies are attached to a fluorescent dye for viewing under a fluorescent microscope.

8

Technique #5

Autoradiography

Radiolabeled hormones are injected into a tissue or animal and the sections taken will reveal sites of absorption and radioactivity.

A technique used to detect a radiolabeled substance, such as a hormone, in a cell or organism, by placing a thin slice of the material in contact with a photographic emulsion, which displays darkened silver grains in response to the radioactive emissions.

9

Technique #6

Blot Tests

A cellular technique that is used to discern if a particular protein or nucleic acid is found in a given tissue.

The various forms of these techniques involve electrophoresis of homogenates of tissues from which proteins are extracted.

Electrophoresis will separate these proteins on the basis of electrical charge.

10

Technique #7

“in-Situ” Hybridization

A technique that will allow examination of gene expression in cells, tissues, or organs are identified for a specific protein.

11

Technique #8

Stimulation Followed With Recordings

Direct electrical stimulation of neuronal pools (brain, spinal cord, or peripheral nerves) can elicit electrical activity in cells and tissues of neurall relevant sites.

Rat with electrodes implanted in the brain to allow stimulation of specific regions of the hypothalamus (a major endocrine secreting region).

12

Technique #9

Pharmacological Techniques

The use of chemical agents that may alter the action or function of a hormone.

The 2 major groups are:
AGONISTS – hormone mimics
ANTAGONISTS – hormone blockers

These compounds can be administered to an animal in a variety of ways, but the two most common forms are:

CANNULATION – a form of permanent form of injection tube is implanted in a target region. Used typically for multiple administrations of a pharmacological agent.

SIMPLE INJECTION – using syringes to administer a single dose of a pharmacological agent

13

Technique #10

Anastomosis

An older technique whereby the blood systems of two different animals is interconnected to study the endocrine systems of the two animals.

14

Technique #11

Microdialysis

Much like kidney dialysis, it is a technique that allows the administration of very minute quantities of neurotransmitters, hormones and/or other pharmacological agents into a conscious animal.

But the experimental benefit is that samples (chemical or electrical) from the site are also possible.

15

Technique #12

Brain Imaging

Scanning techiques of various forms that are used to remotely monitor and test the activity of body structure function, esp. that of the brain.

There are several types of these devices including:

Positron Emission Tomography: (PET): will show functioning of brain regions in real time.

Computer Assisted Tomography (CT) – uses x-rays to give a 3-D image of the brain within a particular plane of space.

Magnetic Resonance Imaging (MRI) - using non-ionizing radiation energy to see images similar to CT scans.

16

Technique #13

Genetic Manipulations

Engineering knockout mice

17

Technique #13

Microarrays

This tool is capable of showing the expression (activity) of genes within an animal’s genome.

AKA, "Gene Arrays"


Leptin Example:
Both mice have a defective "ob" gene, resulting in development of obesity.
The normal-weight mouse was given daily injections of the leptin protein, the protein that the "ob" gene encodes, to rescue the effects of its mutation.

18

Histology!!!

>>>>

19

Optogenetics!!!

>>>>>

20

WHAT ARE HORMONES ?

Chemicals produced and released in very small amount by ENDOCRINE glands into the bloodstream

Hormones are not released constantly but instead are released in spurts (pulsatile secretion)

Travel some distance to target organs or tissues

Target cells have specific receptors

Regulates cellular events that lead to activation of enzymatic pathways or to effects on gene expression and protein synthesis

21

Principal actions of hormones:

Metabolism
Growth
Developmental Processes
Behavior

22

Hormonal Communication

1. Uses hormones

2. Released into circulatory system

3. Travels long distances (1mm-2m)

4. Can travel anywhere in the body

5. Slow, graded

6. Mediate long-term processes

7. Little voluntary control

Think blood

23

Neural Communication

1. Uses neurotransmitters

2. Released locally into synapse

3. Travels short distances (20-30 nm)

4. Can travel only along neural tracts

5. Fast, all or none

6. Mediates fast changes

7. Some voluntary control

Think action potentials..

24

Endocrine system

Consists of endocrine glands which have cells that release chemical messages (i.e. hormones) into the blood stream

Endocrine effects as contrasted with:
- Autocrine
- Paracrine

Not mutually exclusive:
A hormone can act in an autocrine, paracrine, and endocrine fashion.

25

Autocrine

Pertaining to a signal secreted by a cell into the environment that affects the transmitting cell.

Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger (called the autocrine agent) that binds to autocrine receptors on that same cell, leading to changes in itself.

26

Paracrine

Paracrine signaling is a form of cell-cell communication in which a cell produces a signal to induce changes in nearby cells, altering the behavior or differentiation of those cells.

27

Endocrine Glands

Hypothalamus

Pineal Gland

Pituitary Gland

Thyroid Gland

Adrenal Glands

Pancreas (Islets of Langerhans)

Gonads

28

Hypothalamus

Part of the diencephalon, located just below the thalamus.

Important in the regulation of autonomic & endocrine functions.

The hypothalamus consists of several collections of nerve cell bodies (i.e., nuclei),

Regulates endocrine function by releasing neurohormones into the hypothalamic–pituitary portal system and by releasing hormones into the circulation of the posterior pituitary gland.

In the Hypothalamus' median eminence, specialized neurons called neurosecretory cells secrete neurohormone (hormones released from a neuron) into the blood vessels of the pituitary

29

Pineal Gland

An endocrine gland (also called the epiphysis), located in between the telencephalon and diencephalon

Secretes melatonin, a hormone important inthe regulation of daily and seasonal cycles.

30

Anterior Pituitary

Front part of the endocrine gland.

Extends from the base of the brain.

Secretes a number of TROPIC hormones in response to hormonal signals from the HYPOTHALAMUS.

Receives little, if any neural input

Neurohormones from the hypothalamus reach the anterior pituitary via the PORTAL BLOOD SYSTEM

Causes release of tropic hormones that stimulate various physiological processes either by acting directly on target cells or by causing other endocrine glands to release hormones.

31

Tropic hormones

Tropic hormones are hormones that have other endocrine glands as their target.

Most tropic hormones are produced and secreted by the anterior pituitary.

32

Posterior pituitary

The rear part of the endocrine gland that extends from the base of the brain.

Stores & releases OXYTOCIN and VASOPRESSIN (or some variant of these nonapeptide hormones) which are produced in the hypothalamus.

Hormones are secreted directly from neurons into the blood

33

Thyroid Gland

A double-lobed endocrine gland located on or near the trachea or esophagus in vertebrates.

Secretes several hormones important in metabolism, including triiodothyronine and thyroxine.

34

Adrenal Glands

Paired, dual-compartment endocrine glands in vertebrates consisting of a medulla and a cortex.

Epinephrine & Norepinephrine are secreted from the medulla.

Steroid hormones are released from the cortex.

35

Adrenal Medulla

The inner portion of the endocrine organ that sits above the kidneys.

Secretes Epinephrine & Norepinephrine.

36

Adrenal Cortex

The outer layer(s) of the endocrine organ that sits above the kidney.

Secretes steroid hormones.

37

Pancreas

A compositevertebrate gland with both endocrine and exocrine functions.

The pancreas is located within the curve of the duodenum behind the stomach & liver

Secretes digestive enzymes (exocrine function).

Secretes insulin, glucagon, and somatostatin (endocrine function).

Also secretes bicarbonate.

38

Islets of Langerhans

Islands of endocrine tissue nested throughout the exocrine tissue of the pancreas.

There are 4 different cell types among the islets of Langerhans, each of which secretes a different type of protein hormone.

39

Steroid Hormones

Fat soluble (i.e. can easily move through cell membranes)

NOT soluble in water!!!
Thus, require carrier proteins for transport through the blood to their target tissue

Receptors located inside the cells (cytosol or nucleus)

Have slow but lasting effects

Carrier protein example:
Sex hormone binding globulin (SHBG)

A class of structurally related fat-soluble chemicals that are derived from cholesterol.

Characterized by three 6-carbon rings plus one conjugated 5-carbon ring.

40

Examples of Steroid Hormones:

Steroid hormones can be grouped into 5 groups by the receptors to which they bind:

Glucocorticoids
Mineralocorticoids
Androgens
Estrogens
Progestogens

Vitamin D derivatives are a 6th closely related hormone system with homologous receptors.

41

Protein & Peptide Hormones

Made up of individual amino acids:
Peptide (small)
Protein/polypeptide (large)

Stored in vesicles of endocrine cells

Released into circulation by exocytosis

Soluble in blood!!!s
Don't require carrier proteins.

Act rapidly (i.e. seconds to minutes)

Can vary in their sequence of amino acids

42

Examples of Protein & Peptide Hormones

Neurohormones of the Hypothalamus

Tropic Hormones of the Anterior Pituitary

Posterior pituitary hormones

Parathyroid hormone

Calcitonin

Gastrointestinal hormones

Ghrelin & Leptin

Pancreatic hormones

43

How are hormones regulated?

The most common form of hormone regulation is NEGATIVE FEEDBACK

NEGATIVE FEEDBACK:
The product of the target tissue feeds back on the source of the hormone to stop hormone production.

POSITIVE FEEDBACK:
The production of hormone stimulates additional hormone production.

44

Sexual differentiation

the process of becoming a male or female

45

List the Order of Sexual Differention

1. Chromosomal sex

2. Gonadal sex

3. Hormonal sex

4. Morphological sex

5. Behavioral sex

46

Chromosomal sex:

Female: XX, homogametic

Male: XY, heterogametic

47

Gonadal sex:

Females: ovaries, eggs

Males: testes, sperm

Related to gametic sex.

48

Hormonal sex:

Female: high estrogen, low androgen

Male: high androgen, low estrogen

49

Morphological sex:

differences in body type, CNS, and effector organs (i.e., muscles)

50

Behavioral sex:

discriminated on the basis of male and female typical behaviors

51

REVIEW: Hormonal Control of Development

!!!!!!!!!!

52

Organizational/Activational Hypothesis

Behavioral sex differences result from:

1. Differential exposure to hormones that act early in development to organize neural circuitry underlying sexually dimorphic behaviors

2. Differential exposure to sex steroid hormones later in life that activate the neural circuitry previously organized

53

ORGANIZATIONAL

Occurs before the brain matures

Critical period

Relatively permanent

54

ACTIVATIONAL

Adulthood

No sensitive period

Transitory (not permanent)

55

Gonadal hormones and developmental apoptosis:

regional specificity!!!!!!

Estradiol decreases apoptoses in the SDN

Estradiol increases apoptoses in the AVPv

56

A sampling of human sex differences in cognition:

Males Better

Spatial tasks

Aim

57

A sampling of human sex differences in cognition:

Females Better

Verbal tasks

Noticing minute details and differences

58

Male reproductive behavior

Divided into 2 phases:
Appetitive: courtship
Consummatory: copulatory behavior

“Males expend much more time & energy seeking copulation than actually copulating” …

59

Maintenance vs Restoration of Sex:

Individual Differences in Behavior

Hypothesis:
Animals with high sex drive had higher Testosterone levels than animals with low sex drive

Individual differences in sexual behavior are NOT determined by individual differences in androgen levels

60

Maintenance vs Restoration of Sex:

Maintenance: given Testosterone immediately after castration

Restoration: Testosterone treatment began after all sexual behaviors stopped

Amount of Testosterone necessary to restore full sexual behavior in castrated males is greater if the treatment begins after all sexual behavior stops than if it begins immediately after castration

Restoration regimen requires higher doses because androgen receptors decrease in number if not maintained by circulating androgens. Musculature atrophies too.

61

Evidence that MPOA regulates male sexual behavior

Lesions of the MPOA abolishes sexual behavior, but sexual motivation is unaffected****

Electrical stimulation of the MPOA accelerates ejaculation

Autradiographic studies have shown that the MPOA contains androgen & estrogen receptors

Using in situ hybridization, aromatase mRNA has been detected in the MPOA

Implants of Testosterone into the MPOA of castrated males facilitates sexual behavior, but not if given with an aromatase inhibitor

Activated by copulatory stimuli as detected by the immediate early gene Fos******

62

Dopamine and male sexual behavior

Major effect of POA lesions: Destroying connections to dopaminergic neurons in PAG and VTA.

Dopamine (DA) agonists can provide some restoration.

In intact rats, Dopamine agonists facilitate mating behavior, whereas antagonists suppress mating.

Microdialysis studies show that extracellular Dopamine in MPOA increases in response to cues from an estrous female

63

Estrous females

Will seek out males, initiate copulation and prefer to remain in close proximity to males

Are very attractive to males

Males prefer to mount

Are receptive and will permit mating to occur

64

Anestrous females

Will NOT seek out males, initiate copulation, or remain in close proximity to males

Are not attractive to males

Males are unlikely to mount

Are NOT receptive and will NOT permit mating to occur

65

Estrous Cycle

Estrous cycle:
Cycle between mating and non-mating conditions in female (4-5 days in rats)

4 stages:
Diestrus 1, Diestrus 2, Proestrus (behavioral estrus), Estrus

Mating behavior coupled in
time with ovulation

Estrogen & progesterone:
Ovulation .
Affect the brain to influence the female’s behavior and induce receptivity

66

Proestrus

"behavioral estrus"

Ovulation occurs

Estrogen & Progesterone peak at their HIGHEST.

Progesterone increases more steeply, dramatically in this stage than Estrogen.

67

Estrus

Occurs after ovulation, after pro-estrus.

Marked by fallen levels of Estrogen & Progesterone

68

Proceptivity

Female Appetitive phase

Reflects underlying motivational state

Sexually solicitous behavior that initiates sexual union, but is not copulatory behavior per se:
E.g. hopping & darting, ear wiggling in rats; solicitations in non-human primates

High concentrations of Estrogen facilitate proceptive behavior

69

In OVX rhesus monkeys, Estrogen increases proceptivity in absence of male interest (non-breeding season)

ACTIVATIONAL

70

Receptivity

Female Consummatory phase

Those female reactions that are necessary & sufficient for fertile copulation with a male

Indicated by a species-specific mating posture in all nonhuman primates, e.g. lordosis in rodents

ESTROGEN is important in receptivity

Female primates are able to copulate at all stages of their ovarian cycles

Suggests that hormones do not influence female receptivity

But…hormones do play a role in receptivity under certain social conditions

71

Ventromedial nucleus of the hypothalamus (VMN) and LORDOSIS

Lesions of the VMN abolishes lordosis

Electrical stimulation of the VMN induces lordosis

Destruction of afferent & efferent fibers reduces the frequency of lordosis

72

Ventromedial nucleus of the hypothalamus (VMN) and ESTROGEN

Estrogen implanted into VMN induces receptivity

Estrogen increases the production of Progesterone receptors (PR)

If Estrogen primed rats receive infusion of Progesterone Receptor antisense oligonucleotides into VMN (i.e., block production of PR) then lordosis can’t be elicited

73

Human Proceptivity

Some studies have shown that sexual interest peaks around the time of ovulation.

Although the ABILITY to copulate is not linked to hormones in humans, the MOTIVATION to copulate appears to be linked to androgens, not estrogens:

Blood concentrations of androgens fluctuate during the menstrual cycle peaking mid-cycle when sexual interest peaks

Plasma Testosterone levels in women positively correlated with sexual desire

Treatment with low doses of androgens can increase libido in postmenopausal women

Both testosterone & estradiol levels in females are positively correlated with self-reported orgasms

74

Hormones Regulate the Onset of
Maternal Behavior!!!!!!

How do hormones promote
maternal behavior? ???

Think APPROACH vs. AVOIDANCE

75

Pups Are Highly Rewarding to Postpartum Females

.....

76

Maintenance of Maternal Behavior

Depends on somatosensory /tactile feedback that a dam receives from the pups

Anesthetizing/severing the nerves that innervate the mouth ----> nest building, licking, and pup retrieval are reduced or abolished

Anesthetizing/removing the mother’s nipples ---> failure to nurse pups

77

Neural Networks Involved in Maternal Behavior

Maternal behaviour has several elements:
nest-building, gathering the young, nursing, cleaning, protecting, and non-aggression towards the young.

Different, but interconnected, neural networks are responsible for each element.

The medial preoptic area (mPOA) has a central role in the regulation of these maternal behaviors.

Hormone priming of the mPOA is mediated by estrogen, progesterone, prolactin, and oxytocin. Receptors for these hormones are upregulated.

Oxytocin is released in the brain during child birth and acts on oxytocin receptors in the mPOA, nucleus accumbens (NAcc), ventral tegmental area (VTA), paraventricular nucleus (PVN), olfactory bulbs, lateral septum (LS), and amygdala.
This leads to the rapid initiation of maternal behaviour.

The aversion to pup odour that is evident in non-pregnant and early-to-mid-pregnant rats is mediated by olfactory bulb projections to the cortical (CoA) and medial (MeA) amygdala, and then to the anterior hypothalamus (AH) and periaqueductal grey (PAG).

Activation of the hormonally primed mPOA and the adjacent vBNST on the one hand overrides aversive responses to newborn odor, and on the other hand activates the meso-limbic dopaminergic reward circuitry (VTA and NAcc).

The withdrawal at birth of inhibitory mechanisms, in particular in the mPOA, also facilitates maternal behavior.

78

mPOA sends GABA to inhibit the aversion circuit in new moms

mPOA sends Glutamate to the lactation circuit of new moms

79

MPOA and maternal behavior

Lesions of MPOA disrupt maternal behavior

Increased neural activity as measured by c-fos in the MPOA of dams

Has receptors for Estrogen, Prolactin, and Oxytocin which increase in number during pregnancy

In virgin females, infusion of these hormones into the mPOA will induce maternal care

In postpartum females, blocking receptors for these hormones in the MPOA will disrupt maternal behavior

80

Human Hormones During Pregnancy

High estrogens & 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 & cortisol throughout gestation (to suppress immune reaction of the mother toward the fetus)

81

_________ increases positive interactions (gaze, vocalizations, positive affect, and affectionate touch) as assessed during a 15 min mother-infant interaction.

Oxytocin increases positive interactions (gaze, vocalizations, positive affect, and affectionate touch) as assessed during a 15 min mother-infant interaction

82

Handgrip force reaction to infant crying reduced in nulliparous women given intranasal ____ suggesting that _____ may inhibit parental hostility

Handgrip force reaction to infant crying reduced in nulliparous women given intranasal Oxytocin suggesting that Oxytocin may inhibit parental hostility

83

Hormones in fathers

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

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

Decreased Testosterone & Cortisol also linked to paternal care:
Saliva samples from first time father recruited from prenatal classes compared to controls – general population, matched for age, time of day, season

84

Overlap between romantic and maternal love activation patterns in brain?

Found overlapping areas of brain activation including the Putamen, Caudate Nucleus, and the Medial Insular and Anterior Cingulate Cortex.

This emphasizes the fact that affiliative behaviors evolved from parental behaviors.

Interestingly, brain regions that showed the most activation either are part of the brain’s reward circuitry (mesolimbic and NA) or contain a high density of Oxytocin receptors and Vasopressin Receptors.

85

Hormones underlying social affiliation:
Oxytocin (OT)

Using autoradiography the Oxytocin receptors of monogamous and polygamous voles have been characterized.

Species difference also true for vasopressin V1aR too

Prairie Voles are associated with long-term Pair Bonds

86

Hormones underlying social affiliation:
Testosterone and Voles

There are strong correlations among blood Testosterone concentrations and testis size, sperm counts, and social systems (monogamy vs polygamy)

These lower levels of Testosterone could possibly indirectly mediate approach behaviors that are needed in order to care for the offspring.
Hormones that evoke affiliation thus serve as a means of bringing about this cooperation.

This does not mean that if you give supplemental Testosterone to a monogamous vole that it is going to go out and become promiscuous just as castration of a polygamous vole will not make it monogamous.

87

Monogamous
(prairie voles)

Lower circulating testosterone concentrations

Lower sperm numbers

Smaller testes

88

Polygamous
(meadow & montane voles)

Higher circulating testosterone concentrations

Higher sperm numbers

Larger testes

89

Oxytocin and reward system:

Both ______ and ______ show greater activation to partner than unfamiliar if Oxytocin given 1st

Oxytocin and reward system:

Both ventral tegmental area and nucleus accumbens show greater activation to partner than unfamiliar if Oxytocin given 1st

90

Hormones that mediate _____ are similar to the ones that mediate ______ behaviors

Hormones that mediate affiliation are similar to the ones that mediate parental behaviors

91

The underlying mechanisms of affiliation probably evolved from the same neuronal mechanisms that mediate _____ behavior

The underlying mechanisms of affiliation probably evolved from the same neuronal mechanisms that mediate parental behavior

92

Most hormones associated with affiliation reduce stress or fear of social contact – ______ – and allows them to come together and engage in social behavior and mating behavior

Most hormones associated with affiliation reduce stress or fear of social contact – animals adaptive response – and allows them to come together and engage in social behavior and mating behavior

93

Aggression: organizational/activational

???????

In large part, organized

Aggression is organized perinatally by androgens but also requires the presence of androgens after puberty in order to be fully expressed.

94

Olfactory cues are processed by the Olfactory Bulb and processed by the ______.

Stimulus ultimately ends in the _____ which promotes species-specific aggression.

Olfactory cues are processed by the Olfactory Bulb and processed by the Medial Amygdala.

Stimulus ultimately ends in the periaquaductal grey (PAG) which promotes species-specific aggression.

95

Stress can inhibit aggression via inhibitory inputs from the _____, the _____, and the ______.

Stress can inhibit aggression via inhibitory inputs from the orbital frontal cortex (OFC), the hippocampus, and the paraventricular nucleus (PVN).

96

Aggression is typically evoked by vocal or visual signals.

Activation of the ____ results in activation of the BNST and anterior hypothalamus, which in turn activate the PAG for _______ output.

Aggression is typically evoked by vocal or visual signals.

Activation of the Medial Amygdala results in activation of the BNST and anterior hypothalamus, which in turn activate the PAG for aggressive output.

97

The orbital frontal cortex (OFC) is important for the ______.

Inhibitory inputs from the OFC might ______ by reducing responsiveness in the amygdala.

The orbital frontal cortex (OFC) is important for the interpretation of social cues, and inhibitory inputs from the OFC might inhibit aggression by reducing responsiveness in the amygdala.

98

Aggression is typically evoked by vocal or visual signals.

Activation of the MEA results in activation of the BNST and anterior hypothalamus, which in turn activate the PAG for aggressive output.

Most homeostatic systems operate like a thermostatically controlled heating & 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 point, the air conditioner is engaged

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”)

99

Thirst

Low blood volume???

Hypovolemic thirst.

Bleeding out reduces blood volume.

100

Cellular dehydration due to high extracellular salt concentration ???

Osmotic Thirst

101

REVIEW: Glucose homeostasis

?????

102

Type I Diabetes

Insulin dependent mellitus

Autoimmune disorder in which the β 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

103

Type II Diabetes

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, it can cause the pancreas to stop producing insulin, requiring the use of exogenous insulin treatment

104

Hypothalamus Regulates Food Intake

Current model focuses on the Arcuate Nucleus, which
Has two neuronal circuits with opposite effects:

1. Feeding Stimulatory Circuit (Anabolic) produces 2 orexigenic peptides that stimulate food intake, reduce metabolism, and promote weight gain:
NPY (neuropeptide Y)
AgRP (agouti related protein)

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

105

orexigenic substances

An appetite stimulant

Increases hunger, and therefore enhances food consumption.

106

Feeding Stimulatory Circuit

Anabolic

Produces 2 orexigenic peptides that stimulate food intake, reduce metabolism, and promote weight gain:
NPY (neuropeptide Y)
AgRP (agouti related protein)

Arcuate Nucleus

107

Feeding Inhibitory Circuit

Catabolic.

Produces 2 signaling molecules that inhibit food intake, increases metabolism, and promotes weight loss:
POMC produces α-MSH
CART (cocaine- & amphetamine-regulated transcript)

Arcuate Nucleus

108

Leptin from adipose tissue is a satiety signal.

Stop eating!

Leptin receptors on arcuate neurons.

Turn off feeding stimulatory circuit, turn on feeding inhibitory circuit

109

Other signals besides leptin & insulin control hypothalamic feeding centers

Ghrelin is only one of many many signals that regulates hunger & feeding.

Ghrelin from stomach activates feeding stimulatory circuit, inhibits feeding inhibitory circuit.

110

De Marian found in 1800s that tension-relaxation pattern of heliotropic plants persists even if plants isolated from _______ (sun etc.)

De Marian found in 1800s that tension-relaxation pattern of heliotropic plants persists even if plants isolated from exogenous factors (sun etc.)

ENDOGENOUS?

111

Rhythmic changes that continue at about a 24-hr cycle in the absence of external cues

Body Temperature.
Cortisol Secretion.
Sleep & Wakefulness.
Growth Hormone.
Body Temperature.

112

Tau

In the absence of time cues, most circadian cycle period in humans lasts approximately 24.2 to 24.9 hours

This length of individual rhythm is called Tau (τ)

113

Evidence that biological rhythms are set by endogenous factors

Isolation experiments have been key.

Constant darkness or dim light studies.

Animals maintained in space (away from tides, light/dark cues, etc) maintain a rhythm on their own.
E.g., Fiddler crabs, rodents, insects, birds, primates

Individual animals reared & maintained in exactly the same conditions show subtle differences in rhythms that persist

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

114

Entrainment

the process of resetting the biological clock (or keeping it aligned)

115

zeitgeber

The stimuli that an organism uses to synchronize with the environment.

means “time-giver” in German

Without a zeitgeber, drift occurs, but still stays close to a 24-hr period.

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Endogenous rhythm period

Tau (τ)

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master biological clock

Suprachiasmatic nuclei (SCN)

A collection of cell bodies in the hypothalamus.

Located above the optic chiasm.

Contains one or more biological clocks responsible for the temporal organization of many physiological & behavioral parameters.

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Suprachiasmatic nuclei (SCN)

Details, details.....

The SCN electrically more active during light period of cycle, as measured using electrophysiology or autoradiography for glucose usage.
This is true in both nocturnal & diurnal species.

Individual cells of the SCN show precise changes in activity across circadian cycle

The SCN is necessary for endogenous (uncued) circadian rhythms

With light cues or other schedules, rhythm can be maintained somewhat

In constant dim light, entrained rhythm goes away

Suggests cues can mostly overcome trouble with endogenous clock as long as they are available

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In _______, entrained rhythm goes away

In constant dim light, entrained rhythm goes away

120

Retinohypothalamic Pathway (RHT)

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

Most of these retinal ganglion cells contain the photopigment melanopsin (blue light)

Glutamate is released into SCN when RHT is activated by light

Glutamate ‘jump starts’ production of PER & TIM to suppress sleep behavior

In other species, such as many birds, the pineal gland is a central clock.
The pineal gland is not the master clock in mammals, but it is still important to rhythms.

121

In some reptile and bird species, the ______ is a central clock

pineal gland

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Melatonin

the hormone of darkness

released by pineal gland in response to signals from the SCN (via an indirect pathway involving the sympathetic chain ganglia releasing norepinephrine)

Production of melatonin is inhibited by light coming in via RHT.
This is true in both diurnal & nocturnal species.

Melotonin tells the body it is dark, NOT whether we should be asleep or awake, breeding or not breeding.

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CHRONOTYPE:

Tau + Melatonin curves

Different species (and even different individuals) have slightly different cycle lengths (Tau)

Night owls vs. larks

Individuals pattern of hormone secretion also key.
Early morning types have more rapid decline in melatonin levels following nighttime peak.