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Questions and Answers
What time does melatonin secretion start?
At which time does the body experience the deepest sleep?
What is the main function of the suprachiasmatic nucleus (SCN)?
Which theory suggests that sleep is necessary for repair and regeneration of the body?
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Young individuals are typically characterized as which type of chronotype?
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What does the elimination theory of sleep focus on?
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Which type of sleep is essential for neural reorganization and brain structure growth?
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Which process describes the selective strengthening and weakening of synaptic connections during sleep?
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What is the primary role of the energy conservation theory?
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What is the consequence of low light exposure on melatonin production?
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What is the primary function of aromatase in the context of male brain development?
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Which of the following is NOT a secondary sex characteristic typically associated with male development?
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How do male and female brains differ in terms of gray and white matter?
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What does the term 'phenotype' refer to in biological terms?
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What role does alpha fetoprotein play during fetal development?
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Which part of the brain is associated with social cognition and interpersonal judgment, especially in females?
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What effect do higher androgen levels during fetal development have on male brain structure?
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Which structure is directly involved in the release of hormones as part of the Hypothalamic-Pituitary-Gonadal (HPG) axis?
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What primary role does oxytocin play in maternal bonding?
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Which hormone is primarily responsible for stimulating lactation?
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What is the effect of Pitocin during labor?
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What does the anterior pituitary release in response to gonadotropin-releasing hormone?
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What triggers ovulation in the menstrual cycle?
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What does follicle-stimulating hormone (FSH) primarily promote?
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How do estradiol levels fluctuate during the menstrual cycle?
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What role does luteinizing hormone (LH) play in males?
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What is indicated by the presence of continuous slow-wave sleep in the cortical EEG of a cerveau isolé preparation?
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Which wave pattern is associated with deep sleep, particularly in stage 3 of the sleep cycle?
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What is the primary function of progesterone during pregnancy?
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What occurs when progesterone levels drop significantly?
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Which of the following neurotransmitters is primarily involved in maintaining arousal and wakefulness?
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What is the main symptom of narcolepsy characterized by sudden muscle weakness?
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What is the primary source of estrogen in females during the ovarian cycle?
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What characterizes the different stages of non-REM sleep regarding duration and frequency?
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During which phase does the Graafian follicle release an oocyte?
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Which hormone is synthesized and released by developing testes that prevents the formation of female reproductive structures?
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What is the result of the Lee-boot effect in female mice?
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What is an effect of high levels of GABA during sleep?
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What is the role of the corpus luteum after ovulation?
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What might trigger the Bruce effect in female mice?
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In the context of sexual development, what happens if the SRY gene is absent during early fetal development?
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Which medication is primarily used to help reduce excessive daytime sleepiness in narcolepsy?
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How does the Whitten effect impact female mice’s reproductive cycles?
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What describes the role of sleep spindles during sleep?
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What hormone primarily prevents ovulation in the combination birth control pill?
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Which condition is associated with mutations in the SRY gene leading to XY females?
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What is likely to be the outcome when a female mouse is housed continuously with other females?
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What happens to the corpus luteum if fertilization does not occur?
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What primary change occurs during the 'wake' state of the sleep-wake flip-flop?
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What effect do male pheromones have on young female mice in terms of puberty onset?
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How does a lack of 5-alpha reductase affect sexual development before puberty?
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Which hormone is primarily responsible for thickening the uterine wall during the secretory phase?
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What aspect of REM sleep is crucial for remembering dreams?
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What brain wave pattern is typically observed during a highly focused mental activity?
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Study Notes
Circadian Rhythm
- Our bodies have a natural 24-hour cycle called the circadian rhythm. This cycle regulates our sleep-wake patterns, hormone release, and other bodily functions.
- Peak coordination occurs between 2:30 - 3:30 PM
- Peak reaction times are between 3:30 - 4:30 PM
- Cardiovascular deficiency and muscle strength peak between 5:00 - 6:00 PM
- Blood pressure is highest between 6:30 PM - 7:00 PM
- Body temperature is highest between 7:00 - 8:00 PM
- The production of melatonin, a sleep-regulating hormone, begins around 9:00 PM
- Bowel movements are suppressed around 10:30 PM
- The deepest sleep occurs between 2:00 - 4:00 AM
- Body temperature is lowest between 4:00 - 5:00 AM
- Blood pressure rises sharply between 6:45 - 7:30 AM
- Melatonin stops being released from the pineal gland around 7:30 AM
- Our body is most likely to need a bowel movement from 8:30 - 9:00 AM
- The highest testosterone secretion occurs around 9:00 AM
- Alertness is highest from 10:00 - 11:00 AM
The Suprachiasmatic Nucleus (SCN)
- The SCN is the biological clock of the body, located in the hypothalamus. It is responsible for regulating circadian rhythms.
- Light stimulates the SCN, which tells the pineal gland to decrease melatonin production.
- This happens via retinal ganglion cells releasing melanopsin that stimulates the SCN
- Low light levels result in increased melatonin production.
Chronotype
- Chronotype is an individual's natural preference for sleep and wake times, influencing their alertness levels.
- Chronotype changes with age
- Young people are often "night owls" and perform better in the afternoon and evening
- Older people generally prefer to be "morning larks" and perform better in the morning.
Sleep Theories
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Recuperation theories: Sleep helps restore and repair our bodies.
- Restorative theory: Sleep is crucial for repairing and regenerating the body. This includes muscle repair, tissue growth, protein synthesis, and the release of growth hormone.
- Elimination theory: Sleep helps eliminate waste products in the brain. This includes strengthening certain synaptic connections and weakening or eliminating unnecessary ones.
- Brain plasticity theory: Sleep helps to improve neural reorganization, grow new neurons, and support brain structure development.
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Adaptation theories: Sleep serves to protect us from danger and conserve energy.
- Immobilization theory: Sleep is an instinctive response that keeps individuals inactive and safe during the least efficient part of the day or night.
- Energy conservation theory: Periods of inactivity during sleep help conserve energy after engaging in survival activities.
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Activation synthesis theory: Dreams result from the activation and synthesis of specific brain regions.
Functions of Slow-Wave Sleep
- Promotes survival.
Brain function: Sleep
- The cerveau isolé preparation displays a pattern of continuous slow-wave sleep.
- A lesion damaging the core of the reticular formation at the mid collicular level, but leaving sensory fibers intact, results in a cortical EEG indicative of continuous slow-wave sleep.
- Electrical stimulation of the pontine reticular formation desynchronizes the cortical EEG and awakens sleeping cats.
- The encéphale isolé preparation displays a normal sleep-wake cycle of cortical EEG activity.
- Findings indicate a wakefulness-producing area in the reticular formation between the cerveau isolé and encéphale isolé transections.
- Stage 1 of sleep (NREM, alpha to theta waves) lasts about 1-7 minutes and involves a slowing of muscle activity.
- Stage 2 of sleep (NREM, theta waves, sleep spindles, K complexes) lasts about 10-20 minutes and represents about 50% of total sleep time.
- Stage 3 of sleep (NREM, delta waves) can last 20-40 minutes and involves deep sleep, with more time spent in this stage earlier in the sleep cycle.
- Transitory Stage 1 is equal to REM sleep.
- Stage 4 of sleep (REM, beta waves, "Paradoxical Sleep") is characterized by dreaming and increases in length as the sleep cycle progresses, taking up 20-25% of the night.
- To remember dreams, one must awaken upon dream completion.
- Each sleep cycle is approximately 1.5 hours.
Brain waves and functions
- Gamma waves (irregular, low amplitude, highest frequency about 30-120 Hz) are associated with hyper-focused, concentrated states.
- Beta waves (irregular, low amplitude, high frequency about 13-30 Hz) are prevalent during a waking state.
- Alpha waves (fairly regular, low amplitude, high frequency, about 8-13 Hz) are commonly associated with meditation.
- Theta waves (low amplitude, moderate frequency, about 4-8 Hz) are a common indicator of sleep.
- Sleep spindles (short bursts of about 12-14 Hz) play a role in inhibiting external stimuli, reducing sensory perception, helping prevent transitions from light to wakefulness, and contributing to memory consolidation and learning.
- K complexes (sudden sharp waveforms) respond to external stimuli, prevent waking, promote sleep preservation, contribute to memory consolidation, and help the brain determine if a stimulus warrants waking.
- Delta waves (high amplitude, low frequency, about 1-4 Hz) display synchronized neuronal activity and are associated with the body's restorative processes.
Arousal and neurotransmitters
- Acetylcholine (Dorsal pons and basal forebrain) plays a role in arousal of the cerebral cortex, with high levels during wakefulness and REM. It projects to the medial pons, thalamus, and cortex and is primarily involved in promoting wakefulness in the pons.
- Norepinephrine (Locus coeruleus) plays a role in attention and vigilance, has a possible role in "behavioral" arousal, and reaches high levels only during wakefulness. The levels are lower during SWS and lowest during REM. It projects to the cortex, thalamus, hippocampus, cerebellum, pons, and medulla.
- Serotonin (5-HT) (Raphe nuclei) reaches high levels during wakefulness and decreases as it descends towards REM. It contributes to cortical and behavioral arousal, plays a role in activating behavior (pacing, chewing, grooming in rodents), and projects to the thalamus, hypothalamus, cortex, hippocampus, and basal ganglia.
- Histamine (Tuberomammillary nucleus) reaches high levels during wakefulness, and levels are low during SWS and REM. It is implicated in the control of wakefulness and arousal and projects to the cortex, thalamus, hypothalamus, basal ganglia, and basal forebrain.
- Orexin (Lateral hypothalamus) reaches high levels during wakefulness and is low during rest and all sleep stages. It ensures the brain remains alert and active, particularly under stimulating/demanding conditions, and increases activity in the brainstem and forebrain arousal systems.
Slow-wave sleep and neurotransmitters
- GABA (Ventrolateral preoptic area) promotes sleep and suppresses alertness and behavioral arousal. High levels are associated with sleep, inhibiting wake-promoting neurons to maintain the sleep state (contributing to REM sleep paralysis). Low levels are associated with wakefulness.
- Adenosine (throughout the day) increases activity in the vlPOA. This peptide is released during high levels of metabolic activity throughout the day.
The Sleep/Waking Flip-Flop
- The "wake state" involves active arousal systems (cholinergic, noradrenergic, serotonergic, histaminergic) and an inhibited vlPOA from brainstem and forebrain arousal systems.
- The "sleep state" involves an active vlPOA and inhibited arousal systems (cholinergic, noradrenergic, serotonergic, histaminergic). The vlPOA sends inhibitory signals (GABA) to the arousal systems, preventing neurotransmitter release, resulting in slow-wave sleep.
Narcolepsy
- Symptoms of narcolepsy include: sleep attacks, cataplexy, sleep paralysis, hallucinations (hypnagogic and hypnopompic), difficulty staying awake, difficulty falling asleep, fragmented sleep, REM sleep intruding into the waking state, and skipping SWS to enter REM sleep quickly.
- Prevalence of narcolepsy is about 1 in 2,000.
- Possible causes of narcolepsy include: a deficiency of the peptide neurotransmitter orexin, mutations in the Orexin B receptor, a complete absence of Orexin (found in 7 out of 9 people with narcolepsy) and an autoimmune response against orexin neurons occurring in adolescence.
Treatments for narcolepsy
-
Stimulants (taken in the mornings) include:
- Ritalin (methylphenidate): dopamine and norepinephrine agonist (reuptake inhibitor)
- Amphetamine: dopamine and norepinephrine agonist (reuptake inhibitor)
- Provigil (modafinil): orexin agonist
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SSRIs and SNRIs (taken later in the day) include:
- Fluoxetine (Prozac, Sarafem, others)
- Venlafaxine (Effexor)
- Atomoxetine (Strattera)
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Tricyclic antidepressants (taken later in the day) include:
- Protriptyline (Vivactil)
- Imipramine (Tofranil)
- Sodium Oxybate (Xyrem) is a CNS depressant that reduces excessive daytime sleepiness and cataplexy. It is a GABA-B receptor agonist taken before bed and again 3-4 hours later in the middle of the night.
Sexual development and behavior
- Male testes produce sperm cells, containing 23 chromosomes.
- Female ovaries produce ova (eggs), containing 23 chromosomes.
- Fertilization occurs when a sperm cell combines with an ovum, forming a zygote.
- XX chromosomes indicate female, while XY chromosomes indicate male.
- The sex determining factor (TDF) or SRY protein initiates the development of testes.
- The presence of TDF at 6 weeks in a genetic female fetus will trigger the development of testes, leading to the production of male hormones.
Swyer Syndrome
- 46, XY genotype
- Prevalence is approximately 1 in 80,000
- 15-20% involve SRY gene mutations or missing segments containing the SRY gene.
46, XX Testicular Disorder
- Involves a translocation of genetic material between chromosomes, resulting in the SRY gene being misplaced onto the X chromosome.
- Prevalence is approximately 1 in 25,000.
Gonad Development
- Primordial gonads of XX and XY individuals are identical at 6 weeks of conception.
- Differentiation occurs in the second and third prenatal months.
- In a female (XX), the cortex of the primordial gonad develops into an ovary in the absence of a Y chromosome.
- In a male (XY), the medulla of the primordial gonad develops into a testis under the influence of the Y chromosome.
Wolffian and Mullerian ducts
- Wolffian ducts develop into male reproductive structures and regress in females due to the absence of testosterone.
- Mullerian ducts develop into female reproductive structures and regress in males due to the presence of anti-mullerian hormone (AMH).
- Sperm matures and is held in the epididymis.
- Testes develop first.
Development of testes
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MIS and testosterone are synthesized and released as the testes develop.
- MIS stops the Mullerian system from developing.
- 5-alpha reductase converts testosterone to dihydrotestosterone.
- 5-alpha reductase is critical for this conversion process.
5-alpha reductase deficiency syndrome
- Characterized by a lack of sufficient 5-alpha reductase.
- Without dihydrotestosterone, male external genitalia cannot grow.
- Genitals will develop once puberty hits due to high levels of testosterone release, which would cause people with this deficiency to develop their external genitalia.
John Money and John/Joan
- Money argued for the socialization theory of gender identity, stating that a child's gender identity is primarily shaped by socialization and environmental influences rather than biological factors.
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David Reimer, born male, was raised female after losing his penis during a botched circumcision.
- He received hormone treatments and psychological therapy to reinforce a female gender identity, but struggled with his female identity, experiencing distress, rejecting it as he matured. He transitioned to a male, underwent surgeries to reverse the assignment, and this case led to reevaluations of the theories of gender identity development.**
- This case ultimately showed that gender identity does have a biological factor.
Primary Sex Characteristics
- Organizational effects of hormones (or lack of) occur during development and lay the groundwork for future behavior and physiological responses.
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Examples include:
- Male pattern baldness (androgen-dependent)
- Menstrual cycle (estrogen and progesterone)
- Hormonal fluctuations impacting brain development and behavioral patterns
Hormonal Effects on Secondary Sex Characteristics
- Activational effects of hormones influence the development of secondary sex characteristics.
- Examples include breast growth in females, facial hair development, voice deepening, and pelvic widening.
Phenotype & Genotype
- Phenotype refers to the physical observable traits of an organism, which are determined by the genotype.
- Genotype represents the genetic constitution of an organism.
Brain Differences
- Female brains have a higher percentage of gray matter, larger hippocampus, and a larger ventral prefrontal cortex.
- These structures are involved in social cognition and interpersonal judgment.
- Female brains also exhibit higher levels of serotonin, dopamine, and GABA.
- Male brains are 10% larger in cerebral hemispheres, and contain a higher percentage of white matter and cerebral spinal fluid.
- Male brains have a larger and more reactive amygdala and a larger hypothalamus.
- These differences might be due to higher androgen levels in males during fetal development.
Brain Masculinization
- Aromatase converts testosterone into estradiol in the cytoplasm, dendrites, and soma.
- The Aromatization hypothesis proposes that certain effects of testosterone in the brain are mediated by its conversion to estrogen.
- Alpha fetoprotein, produced by the placenta and fetal liver cells during fetal development, binds to circulating estradiol and prevents its entry into the brain.
- It does not bind to testosterone.
Hypothalamic-Pituitary-Gonadal (HPG) Axis
- The hypothalamus releases hormones that stimulate the anterior pituitary.
- The paraventricular nucleus and supraoptic nucleus directly release hormones through the posterior pituitary portal.
- These include oxytocin, known as "the love hormone," which facilitates bonding between a mother and infant, stimulates lactation, and is present in high levels after birth and during sexual interaction.
- Pitocin, given to women in labor to stimulate contractions, is similar to oxytocin.
- The anterior pituitary releases gonadotropins, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
- FSH stimulates ova development in females and sperm development in males.
- FSH also increases estradiol production, promotes the maturation of ovarian follicles, and is high at the beginning of the menstrual cycle before decreasing as the dominant follicle matures.
- LH stimulates testosterone secretion from Leydig cells in testes and Theca cells in ovaries.
- LH surges mid-cycle around day 14 and triggers ovulation.
Gonadal Hormones
- Gestagens, like progesterone, are referred to as the pregnancy hormone. They prepare for and maintain pregnancy and are essential for maintaining high levels during pregnancy.
- Progesterone enables a zygote to implant, keeps the placenta attached to the uterine wall, and plays a role in sperm generation.
- Progesterone is primarily produced by the corpus luteum in the ovary after ovulation and peaks in the postovulatory phase after ovulation.
- Androgens include testosterone, which is responsible for bone growth, body hair growth, and sex drive in females, and dihydrotestosterone.
- Androgens are produced by Leydig cells in testes and Theca cells in ovaries.
- Estrogens, including estradiol, are converted from testosterone by aromatase.
- Estrogen in males is involved in erections, while in females it thickens the uterine wall (endometrium) and modulates sex drive.
- Estrogen is produced by developing follicles, rises during the follicular phase, and peaks right before ovulation, followed by a smaller increase in the postovulatory phase.
Hormonal Cycles
- The preovulatory (follicular) phase lasts approximately days 1-14.
- The postovulatory (luteal) phase lasts approximately days 14-28.
- The ovarian cycle starts with the primary follicle, an early stage of follicle development in the ovary during the follicular phase.
- The secondary follicle represents further maturation and is not yet able to be fertilized.
- The Graafian follicle is the fully mature follicle that will rupture and release an egg during ovulation. It is capable of fertilization.
- Ovulation, around day 14, involves the mature follicle rupturing to release the oocyte (egg).
- The corpus luteum forms after ovulation when the empty follicle transforms and secretes progesterone and estrogen.
- The corpus albicans is the result of the corpus luteum degenerating if fertilization does not occur and cannot stimulate hormones.
- The uterine (endometrial) cycle consists of menstruation, the proliferative phase, and the secretory phase.
- Menstruation, lasting an average of 5 days, involves the shedding of the uterine wall due to low estrogen and progesterone levels at the end of the luteal phase. Bleeding occurs when these hormone levels drop, indicating no pregnancy.
- The proliferative phase coincides with rising estrogen levels during the preovulatory phase, where the endometrium begins to thicken in preparation for potential implantation.
- The secretory phase, following ovulation, involves progesterone from the corpus luteum causing the endometrium to further thicken and secrete nutrients, preparing the uterus for potential pregnancy.
- Menstruation repeats if pregnancy does not occur as the corpus luteum degenerates, progesterone levels drop, and the cycle restarts.
Birth Control
- Birth control pills utilize the negative feedback loop between the ovaries and the hypothalamus and pituitary.
- The most effective type is the "combination pill," which delivers both estrogen and progestin for three weeks.
- Estrogen decreases the secretion of FSH, while progestin prevents the secretion of LH.
- Plan B contains levonorgestrel, a progestin, and must be taken within 72 hours (3 days) of unprotected sex.
- Plan B stops the release of the ovum and may prevent implantation if the ovum has already been released.
- Plan B will not prevent pregnancy if the fertilized ovum has already implanted.
- Mifepristone is a progesterone receptor blocker used to end early pregnancy within 70 days or less since the last menstrual period. It works by stopping the pregnancy from continuing and is followed by Misoprostol 24-48 hours later.
- Misoprostol softens and dilates the cervix and stimulates uterine contractions.
Brain Areas Involved in Sexual Behavior
- The medial preoptic area in the hypothalamus regulates male sexual behavior in rodents.
- The ventromedial nucleus in the hypothalamus regulates female sexual behavior in rodents.
- It stimulates arousal and lordosis: posture of female rodent sexual receptivity.
- Castration followed by estrogen administration results in the exhibition of female behaviors.
- Testosterone administered on day 1 followed by testosterone leads to the exhibition of male behaviors.
Social and Environmental Influences on Female Cycles
- The Lee-Boot effect occurs when female mice are housed together without males. It leads to synchronized and often lengthened reproductive cycles, with some females ceasing cycling altogether.
- It is believed to be driven by pheromones released by females that inhibit each other's reproductive cycles when males are absent.
- The Whitten effect occurs when a group of female mice exposed to a male mouse's scent or pheromones after being isolated from males for a period.
- It results in the synchronization of the females' reproductive cycles, which enter the fertile period concurrently.
- This is attributed to male pheromones acting as a stimulant, reactivating and synchronizing the reproductive cycles of females previously experiencing reproductive suppression and asynchrony.
- The Bruce effect takes place when a recently mated female mouse is exposed to the scent of a new, unfamiliar male who is not the father of her current pregnancy.
- The female often terminates the pregnancy via reabsorption of embryos or spontaneous abortion.
- This phenomenon is believed to be an evolutionary strategy as the new male might be more likely to kill offspring sired by another male.
- By ending the pregnancy, the female can rapidly become receptive to the new male and potentially mate with him, ensuring the survival of future offspring under his protection.
- The Vandenberg effect involves the acceleration or delay of sexual maturation in young female mice depending on the presence of adult males or females.
- Exposure to adult males or their pheromones leads to faster puberty for young females.
- Exposure to only adult females or isolation from males can delay puberty.
- Male pheromones likely promote the onset of puberty in young females, potentially as a way to increase the male's reproductive opportunities.
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