Lecture 5

Question 1

Input to Clock?

Answer 1

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Question 2

Where is the Master Oscillator?

Answer 2

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Question 3

What are the outputs from Clock?

Answer 3

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Question 4

Hormones Affect Behavior: Biological Clocks Affect Hormones

Answer 4

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Question 5

Hormones as Output of Biological

Clocks

Answer 5

ANS serves as a pathway of many SCN signals to the periphery

Hormones are another pathway from the clock to the peripheral tissues

The 2 main hormones that carry temporal
information are melatonin and cortisol in humans (glucocorticoids in animals)

Although many hormones show rhythms.
E.g., renin, angiotensin, aldosterone, noradrenaline, insulin, pituitary trophic hormones (prolactin, growth hormone, thyrotropin), T4, T3, atrial natriuretic
peptide, oxytocin, vasopressin, hypothalamic releasing hormones, estrogens, progestins, androgens.

Question 6

Peak daily cortisol concentrations

Answer 6

Peak usually occurs just prior to or immediately after awakening.

Coincides with the onset of locomotor activities in the morning.

Programmed elevation of blood levels of cortisol increases blood pressure and cardiac output prior to the active phase of
the day.

We know that the increased cortisol concentrations are not driven by the increased activity levels, because the same
circadian rhythm is observed in bedridden patients under constant conditions (Aschoff, 1965).

Question 7

Internal Desynchronization of Circadian Rhythms

Answer 7

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Question 8

Daily patterns of testosterone, glucocoorticoid, and melatonin in humans and nocturnal rats

Answer 8

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Question 9

Hormones have many effects on

daily locomotor activity cycles.

Answer 9

Hamsters become active 5 to 10 min after lights-off.

True of males, but only partially true of females.

Female hamsters display an interesting pattern of activity onset that has been termed “scalloping.”

Every 4th night, coincident with estrus, females show a spontaneous phase advance in their activity onset.

Question 10

Estrogen Phase Advances Tau

Answer 10

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Question 11

Estrogens shorten tau

Answer 11

Hamsters are solitary creatures and it has been speculated that the earlier onset of locomotor activity during estrus increases the female’s odds of locating a male.

The scalloping pattern is eliminated by ovariectomy.

Furthermore, estradiol treatment of free-running, ovariectomized hamsters or rats reduces the period of locomotor activity onset, suggesting a direct effect on the clock itself .

Question 12

Other sex steroid hormones affect tau

Answer 12

Progesterone lengthens the period of circadian rhythms, possibly by counteracting the effects of estradiol

Sex steroid hormones can also affect daily
activity rhythms in males.
Castration lengthens tau.
Androgen replacement restores the period of freerunning locomotor rhythms of male mice.

Question 13

Hypophysectomy lengthens tau

Answer 13

Removal of the pituitary gland lengthens tau by ~12min/day

The endocrine sequelae of hypophysectomy are profound.

In addition to disruptions in sex steroid hormone production, alterations in many other endocrine functions occur after hypophysectomy.

In order to separate the effects of hypophysectomy from other endocrine consequences of the surgery, endocrine manipulations of systems mediated by the anterior pituitary have been attempted.

Question 14

Hypophysectomy lengthens tau, cont.

Answer 14

Investigators have focused on the thyroid gland because of its obvious and direct effects on metabolic processes.

Removal of the thyroid gland shortens tau in canaries.
Thyroid hormone replacement therapy results in a corresponding lengthening of tau.

Hypothyroidism induced by the drugs propylthiourea or propylthiouracil is correlated with lengthened taus in hamsters

Question 15

Thyroidectomy lengthens tau

Answer 15

It remains unresolved whether alterations in thyroidhormone secretion per se or exposure to the anti-thyroid drugs accounts for the changes in period lengths.

Injections of TRH directly into the SCN phase advanced wheel running behavior in hamsters (10 or 100 nM doses phase advanced 18 or 35 min, respectively.

These hormonal influences on behavioral and
physiological cyclic phenomena may eventually provide a key to understanding clock functions directly.

Question 16

Neuroendocrine Mechanisms Underlying

Seasonality

Answer 16

There is an extensive literature on the mechanisms regulating seasonal breeding cycles.

The principles of seasonality derived from this literature will serve as a basis for the examination of the sparser information base directly related to seasonal changes in behavior.

Question 17

The mechanisms that regulate seasonal reproductive changes fall into 2 categories.

Answer 17

One set of mechanisms is directly responsible for timing seasonal rhythms and ensuring that they are synchronized to
the annual geophysical cycles.
• In mammals, the pineal gland and its hormone, melatonin, are involved in mediating the effects of day length on the timing of a wide variety of seasonal changes in physiology & behavior

Another set of neuroendocrine mechanisms is directly responsible for regulating changes in the reproductive system.
• Example: changes in the rate or pattern of pituitary hormone secretion are important for driving changes in reproductive hormones.

Question 18

Seasonal modulation of hormones

Answer 18

Seasonal changes in reproductive hormones, especially sex steroid hormones, result in a cascade of seasonal changes in steroid-dependent behaviors.

In photoperiodic mammals, the various seasonal activational mechanisms are influenced by day length, and thus, by the pineal melatonin.

For some species, including sheep (and maybe hamsters), thyroid hormones play a permissive role in the termination of seasonal reproduction.

Question 19

Seasonal aggression

S. jarrovi

Answer 19

Perhaps the most general case for seasonal
regulation of a behavior by gonadal hormones is exemplified by the male mountain spiny lizard, Sceloporus jarrovi, in which a single behavior is largely regulated by testicular androgens during the breeding season in September & October, but is expressed independently of testicular hormones during other phases of the annual
cycle.

S. jarrovi begins to exhibit territorial behavior,
expressed as intermale aggression, during the midsummer phase that precedes mating.

At this time, castration does not result in a decrease in the level of intermale aggression.

During the subsequent reproductive phase, the level of territorial behavior increases; this increase can be prevented by castration and reinstated by androgens.

Castrated mating-phase lizards do not stop showing territorial behavior altogether; rather, aggressiveness declines to a level similar to that exhibited during the earlier, pre-mating phase.

A third condition occurs in this species subsequent
to the mating phase, in which territorial behavior
is completely absent and the animals aggregate,
tolerating close proximity and even physical
contact by members of the same sex.
During this phase, administration of androgens failed to
stimulate aggressive behavior.
It seems that testicular hormones act only to regulate
the intensity of territorial behavior in S. jarrovi and that
other, as yet unknown, mechanisms determine the
overall annual pattern of territoriality.

Question 20

Seasonal aggression

Answer 20

There are many reports of seasonal changes in agonistic and territorial behavior among birds and mammals.

E.g, male starlings (Sturnus vulgaris) form rigorously defended territories during the breeding season.

This territorial behavior is correlated with high circulating levels of androgens.

At the end of the breeding season, blood androgen levels diminish, and territorial behaviors stop.

The reduction in agonistic behavior allows the formation of so-called winter feeding flocks, which appear to confer advantages in predator avoidance and foraging success.

The independence of aggression from androgen in this species has been hypothesized to have evolved because the greatest threat to reproductive success from conspecific males comes during the breeding season, but the greatest need for nest defense comes later in the year, after the young have been weaned and begin seeking nests of their own.

The link between a biological clock and the
resulting behavior has not been made.

Question 21

Seasonal Aggression:

Rodents

Answer 21

Small rodents also display seasonal changes in aggression and territorial behavior.

Microtine rodents (lemmings and voles), and probably most rodent species in nontropical regions, form winter aggregations.

Animals huddling together presumably benefit by reducing their energetic requirements in the winter.

Presumably, the lack of circulating androgens permits the social tolerance necessary for this pattern of behavior to appear.

Question 22

Seasonal aggression

Neotoma fuscipes

Answer 22

In wood rats (Neotoma fuscipes), seasonal changes in aggressive behavior are apparently independent of testicular hormones.

The level of intermale aggression increases during the breeding season in this species, but this seasonal increase in aggression is also observed in males that have been castrated postpubertally.

Also, the increased aggressiveness continues for some time after the breeding season ends.

Question 23

Daily activity patterns

Answer 23

Field observations of several species of microtine rodents (e.g., Microtus agrestis, M.
oeconomus, M. montanus, Clethrionomys gapperi, and C. glareolus) have indicated a
seasonal shift in activity patterns.

These animals tend to be nocturnal during the summer, and diurnal during the winter.

The adaptive function of the seasonal shift in daily activity patterns probably involves energetic savings.

By constraining the majority of its locomotor activity to the daylight hours during the winter, the animal avoids the coldest part of the day; likewise, bouts of activity during summer nights allow the animal to avoid thermal stress or dehydration

Predator avoidance may also contribute to the adaptive
significance of this seasonal trait.

Question 24

Daily activity patterns

Testosterone

Answer 24

Testosterone appears to mediate the seasonal shift in activity patterns in montane voles.

Adult male voles were either castrated or left
intact and maintained in long-day or short-day
conditions.

Testosterone replacement therapy was given to some castrated animals via subcutaneously
implanted Silastic capsules.

Question 25

Daily activity patterns

VOLES

Answer 25

Castrated montane voles increased diurnal and decreased nocturnal wheel-running activity as compared to intact animals.

Voles implanted with testosterone increased nocturnal activity relative to voles implanted with empty capsules.

These results suggest that photoperiod primarily
mediates the dramatic seasonal shift in activity patterns by affecting androgen production.
That is, short-day animals tend to be diurnal and long-day
animals tend to be nocturnal
Other environmental cues such as temperature and food quality and quantity may also affect activity patterns.

Question 26

Daily activity patterns

hamsters

Answer 26

Similarly, the number of daily revolutions made in a running wheel significantly declines when Syrian hamsters are moved from long days to short days.

This decline in locomotor activity can be mimicked in long-day hamsters by castration, and reversed by testosterone replacement therapy.

Castrated male Syrian hamsters treated similarly but maintained on short day lengths do not increase wheel running behavior, suggesting that the neural tissues underlying this behavior become insensitive to steroids in short photoperiod conditions.

Question 27

Brain Size and Function

Answer 27

Seasonal changes in brain weight have been reported for several species of rodents & shrews.
E.g., C. glareolus, C. rutilus, M. oeconomus, M. gregalis, Sorex auraneus and S. minutus)

Brain weights are heavier in summer-captured than in
winter-captured animals
The adaptive function of this seasonal variation in brain weight may involve energetic savings.
• Although the brain constitutes only 2–3% of the total body mass in rodents and insectivores, it uses over 10% of the total energy expended by the animal.
• Minor reductions in brain mass could result in substantial energetic savings.

Question 28

Seasonal Changes in Brain and

Hippocampal Mass in Shrews

Answer 28

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Question 29

Brain Size and Function

water content

Answer 29

A significant part of the seasonal change in brain weight could be attributable to differences in water content.

However, several parts of the brain, (specifically the neocortex and the basal portion of the brain (i.e., the corpus striatum)) show seasonal cytoarchitectural changes in rodents & shrews.

The relative weight of the forebrain declines during the
winter, the relative weight of the hippocampus increases from winter to summer, and the relative weight of the olfactory bulbs, myelencephalon, and cerebellum increases during the winter.

Question 30

Brain Size and Function

sex difference

Answer 30

A sex difference in brain weight is observed among bank voles (C. glareolus) only during the winter months.

Male brains are heavier than female brains at this time.

The absolute and relative weight of the hippocampus is
significantly higher in males than in females throughout the
year, but the difference is most pronounced during the winter

Meadow voles also show seasonal changes in brain weight.
Photoperiod appears to organize the seasonal fluctuation in brain weight in meadow voles

Males kept under short-day conditions have smaller brains
than long-day animals.

Question 31

Brain Size and Function

Rodents

Answer 31

Despite the evidence for seasonal changes in brain weight in rodents, there has been relatively little research investigating seasonal changes in learning among mammalian species.

Winter-trapped voles make more errors and require longer to learn mazes than summer-captured voles

The extent to which this seasonal change is mediated by day length requires further study.

Among reptiles, seasonal torpor appears to interfere with
learning during the winter.

Question 32

Biological Clocks Affect Hormones

Answer 32

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Question 33

Estrous Cycle in Rat

3 slides

Answer 33

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Question 34

Estrous Cycles

Answer 34

Mating behavior in females usually coincides with ovulation.

Because females ovulate periodically, mating behavior is observed in cycles called estrous cycles.

Female mammals are said to be in estrus when they permit copulation.

Cyclic changes in vaginal cytology have been correlated
with changes in ovarian structure and subsequently with
behavior.

In rats, the vaginal estrous cycle consists of 2–3 days of diestrus, followed by a 12–18h proestrous phase, then a 24–36h estrous period.

Behavioral estrus and mating occur near the end of proestrus and end as the vaginal smear becomes estrous.

Ovulation occurs near the beginning of vaginal estrus.