CNS 2

Question 1

• The ear is the organ of
• The external ear consists of the— and – sealed at its end by the –
• Beyond the eardrum is the –, an air-filled space connected to the – by the –
• The inner ear contains the —: – for hearing and the — for equilibrium

Answer 1

1. The ear is the organ of hearing and equilibrium
2. The external ear consists of the pinna and the ear canal, sealed at its end by the tympanic membrane, or eardrum
3. Beyond the eardrum is the middle ear, an air-filled space connected to the pharynx by the Eustachian tube
4. The inner ear contains the sensors: cochlea for hearing and the vestibular apparatus for equilibrium

Question 2

Hearing

1. Sound is
   a) At the peaks of the waves,— and the –; at the troughs the molecules – and the pressure is –.
2. Frequency is the
   a) We perceive frequency as —: low frequencies as — sounds, high frequencies as –
   b) Frequency is measured in
   c) Humans hear sounds in the range
3. Amplitude is
   a) mplitude is the main factor that determines –, the larger the amplitude–
   b) Loudness depends on

Answer 2

1. Sound is pressure waves
   a) At the peaks of the waves, the molecules are crowded together and the pressure is high; at the troughs the molecules are far apart and the pressure is low
2. Frequency is the number of wave peaks
   per second
   a) We perceive frequency as pitch: low frequencies as low-pitched sounds, high frequencies as high-pitched
   b) Frequency is measured in waves per second, i.e. in hertz (Hz)
   c) Humans hear sounds in the range 16–20,000 Hz — ~10 octaves. Acuity is highest 1000–3000 Hz
3. Amplitude is the pressure difference between peak and trough
   a) Amplitude is the main factor that determines our perception of loudness: the larger the amplitude, the louder the sound (for any one sound frequency
   b) Loudness depends on frequency as well, e.g. a sound of 30,000 Hz is beyond the range of human hearing, so it won’t be loud no matter how large its amplitude

Question 3

1. Sound waves vibrate the x
   a) what does x do
2. what conveys vibrations through the middle ear
   a) The eardrum vibrates the ? which moves
   the ? , which moves the ? , which pushes like a piston against the ?, which is a ?
   b) These 3 bones, called the ? are the smallest in the body. They act as a ? system carrying vibrations from the ? to the ?

Answer 3

1. Sound waves vibrate the eardrum
   a) The eardrum separates the outer ear from the middle ear.
2. A chain of small bones conveys vibrations through the middle ear
   a) The eardrum vibrates the **malleus (hammer) **which moves
   the incus (anvil) , which moves the stapes (sturrup), which pushes like a piston against the oval window, which is a a membrane between middle and
   inner ear.
   b) These 3 bones, called the ossicles, are the smallest in the body. They act as a lever system carrying vibrations from the eardrum to the much smaller oval window.

Question 4

1. The oval window leads into the ?, which contains the ?
2. The ?and ? contain ? (a fluid similar to plasma). These 2 ducts communicate at the ?
3. The cochlear duct (scala media) contains ? (similar to intracellular fluid)
4. The oval window ? , setting up waves in the ?
   a) Wave energy enters the cochlea at the ? and exits, eventually, back into the ? through another membrane called the ?
   b) En route, the waves shake the ? which contains the ? (hair cells), though to see those cells we have to zoom in

Answer 4

1. The oval window leads into the cochlea, which contains the receptor cells
2. The vestibular duct (or scala vestibuli) and tympanic duct (scala tympani) contain perilymph (a fluid similar to plasma). These 2 ducts communicate at the helicotrema
3. The cochlear duct (scala media) contains endolymph (similar to intracellular fluid)
4. The oval window vibrates, setting up waves in the perilymph
   a) Wave energy enters the cochlea at the oval window and exits, eventually, back into the middle ear through another membrane
   called the round window
   b) En route, the waves shake the cochlear duct, which contains the auditory receptor cells (hair cells), though to see those cells we have to zoom in

Question 5

1. The organ of Corti sits on the ? and under the ?
   a) The organ of Corti contains the ? which are ? called hair cells. They are ? not neurons, and number ~20,000 per cochlea
   b) Each hair cell has 50–100 ? “hairs” called ?, which extend into ? They bend when ?
2. When its cilia bend toward the longest cilium, the hair cell ?
   a) The hair cell ? and ? activating a ?
   b) Axons of these neurons form the ? which is a branch of ?
3. When its cilia bend away, the hair cell ?
   a) the hair cell ?, so it releases? and doesn’t ?
4. The ? responds to ? at different points
   a) The membrane is ? and stiff near the ? and ? windows, ? and more ? at its other end
   b) High-frequency waves ? the membrane at the ?; low-frequency waves ? the other end. So the brain can deduce the frequency by ?

Answer 5

1. The organ of Corti sits on the basilar membrane and under the tectorial membrane
   a) The organ of Corti contains the auditory receptor cells — mech- anoreceptors called hair cells. They are epithelial cells, not neurons, and number ~20,000 per cochlea
   b) Each hair cell has 50–100 stiff “hairs” called stereocilia, which extend into the tectorial membrane. They bend when waves in the perilymph deform the basilar and tectorial membranes.
2. When its cilia bend toward the longest cilium, the hair cell excites its neuron
   a) The hair cell depolarizes and releases transmitter, activating a primary sensory neuron
   b) Axons of these neurons form the auditory nerve (also called the cochlear nerve), a branch of cranial nerve VIII
3. When its cilia bend away, the hair cell releases less transmitter
   a) he hair cell hyperpolarizes, so it releases less transmitter and doesn’t excite its neuron as much
4. The basilar membrane responds to different frequencies at different points
   a) The membrane is narrow and stiff near the round and oval windows, wider and more flexible at its other end
   b) High-frequency waves maximally displace the membrane at the oval-window end; low-frequency waves maximally displace the other end. So the brain can deduce the frequency by noting which hair cells are most active

Corti layered: Tectorial membrane, hair cell and then basilar membrane

Question 6

what reveals pitch
to the brain

Answer 6

The pattern of membrane motion reveals pitch
to the brain

Question 7

1. Auditory signals pass from X to x
2. x is in the temporal lobe
3. The brain localizes sounds based on x
   a) If a sound is louder in the right ear than in the left then x. Loudness is conveyed by x i.e. x
   b) If the sound reaches the right ear before the left then x

Answer 7

1. Auditory signals pass from each ear to both sides of the brain
2. Primary auditory cortex (A1) is in the temporal lobe
3. The brain localizes sounds based on loudness and timing
   a) If a sound is louder in the right ear than in the left then it is coming from the right side of the head. Loudness is conveyed by firing
   frequency, i.e. louder sounds make auditory sensory neurons fire at a faster rate
   b) If the sound reaches the right ear before the left then it is coming from the right side of the head.

Question 8

3 types of hearing loss

Answer 8

1. In conductive hearing loss, sound can’t be transmitted through the external or middle ear.
2. In sensorineural hearing loss, there is damage to the hair cells or elsewhere in the inner ear. Mammals can’t replace dead hair cells, though birds can. 90% of hearing loss in the elderly (presbycusis) is sensorineural.
3. In central hearing loss, there is damage to the cortex or the path- ways from cochlea to cortex. Typically the patient’s trouble is in
   recognizing and interpreting sounds, rather than in detecting them

Question 9

1. what distinguish conductive from sensorineural loss
2. the Rinne test
3. In the Weber test

Answer 9

1. Clinical tests distinguish conductive from sensorineural loss
2. the Rinne test you hold a tuning fork against the mastoid bone and then beside the ear, and ask when the sound is louder. Normally it is louder through the ear canal. If it is louder through the bone, there is conductive loss
3. In the Weber test you hold the tuning fork to the patient’s forehead, in the midline, and ask in which ear the sound is louder. With
   sensorineural loss, it is louder in the good ear. With conductive loss, it is louder in the bad ear, because it doesn’t have to compete with sounds heard through that ear canal

Question 10

1. Different parts of the X sense head position and motion
   a) The X and X contain hair cells that are activated when X
   b) The X are fluid-filled hoops that detect X, e.g. X
2. Equilibrium pathways project mainly to
   X
   a) X cells activate primary sensory neurons of the X which is a branch of cranial nerve VIII.
   b) These neurons may either X or X, whence they proceed to the X or up through X to X.
   c) Your brain uses vestibular information to X

Answer 10

1. Different parts of the vestibular apparatus sense head position and motion
   a) The utricle and saccule contain hair cells that are activated when the head tilts relative to gravity.
   b) The semicircular canals are fluid-filled hoops that detect head rotation, e.g. when your head turns rightward, the fluid in the tubes sloshes leftward, activating hair cells
2. Equilibrium pathways project mainly to
   the cerebellum
   a) Vestibular hair cells activate primary sensory neurons of the vesti-
   bular nerve, which is a branch of cranial nerve VIII.
   b) These neurons may either pass directly to cerebellum or synapse in the medulla, whence they proceed to the cerebellum or up through thalamus to cortex.
   c) Your brain uses vestibular information to infer your own position
   and motion, and keep you upright

Question 11

1. Hypothalamus and pituitary are in the x
2. The hypothalamus contains x
   a) It is crucial to the control of x, x , x, and x and x responses.
   b) That control always involves x, i.e. processing chemical and neural signals from the body to monitor how well things are working and to detect disturbances.
   c) Some control systems maintain x — keeping some aspect of x (e.g. osmolality) roughly constant despite disturbances. Other control systems x, e.g. in circadian rhythms
3. The hypothalamus exerts its influence x and x
   a) x within the hypothalamus send x to each other and to other parts of the brain.
   b) The hypothalamus also x which it transports down x to the x of the x, where they are released into the blood.
   c) And the hypothalamus makes x that travel through capillaries (the hypophyseal portal system) to the x, where they trigger the release into the blood of other hormones, made in the pituitary

Answer 11

1. Hypothalamus and pituitary are in the diencephalon
2. The hypothalamus contains control centers for many biological systems
   a) It is crucial to the control of feeding, plasma osmolality, body temperature, and sexual and stress responses.
   b) That control always involves negative feedback, i.e. processing chemical and neural signals from the body to monitor how well things are working and to detect disturbances.
   c) Some control systems maintain homeostasis — keeping some aspect of the internal environment (e.g. osmolality) roughly constant despite disturbances. Other control systems vary things through
   time, e.g. in circadian rhythms
3. The hypothalamus exerts its influence neurally and hormonally
   a) Nuclei within the hypothalamus send neural signals to each other and to other parts of the brain.
   b) The hypothalamus also synthesizes hormones which it transports down axons to the posterior lobe of the pituitary, where they are released into the blood.
   c) And the hypothalamus makes releasing hormones that travel through capillaries (the hypophyseal portal system) to the anterior pituitary, where they trigger the release into the blood of other hormones, made in the pituitary

Question 11

Hypothalamic control of feeding

1. Feeding is tightly controlled
   a) Mice fed solutions with different concentrations of nutrients adjust their eating to x e.g. if the nutrient concentration is halved, they eat twice as much.
   b) The x is crucial to this control, e.g. mice with lesions in the x overeat and become obese; those with lesions in the x get thin.
   c) These areas are in turn controlled by two groups of neurons in the x of the hypothalamus: x cells drive feeding, while x neurons inhibit feeding
2. In the x state, x neurons
   encourage feeding
   a) These are neurons in the x nucleus of the hypothalamus which release x), x, and (in the case of some cells) also x
   3.Arc-NPY projects mainly to x
   a) Signals from Arc-NPY cells inhibit neurons in the x of the hypothalamus (), a x or x center, i.e. a center that quells your appetite for food.
   b) Arc-NPY signals excite neurons in the x, a x center.
3. Arc-NPY inhibits x’s action on the x
   a) High activity in the PVN would excite the x, but Arc-NPY inhibits x, so the x receives x
   b) i.e. Arc-NPY acts via PVN to decrease x.
4. The result is reduced x and therefore more x
   a) High sympathetic activity would x, but Arc-NPY x, i.e. Arc-NPY disinhibits fx
5. LH releases x, which drives x and inhibits x
   a) Projections from LH release x at their x, inhibiting x and stimulating x , though the mechanisms by which x affects feeding are not understood in any detail.

Answer 11

1. Feeding is tightly controlled
   a) Mice fed solutions with different concentrations of nutrients adjust their eating to keep their caloric intake consistent, e.g. if the nutrient concentration is halved, they eat twice as much.
   b) The hypothalamus is crucial to this control, e.g. mice with lesions in the ventromedial hypothalamus overeat and become obese; those with lesions in the lateral hypothalamus get thin.
   c) These areas are in turn controlled by two groups of neurons in the arcuate nucleus of the hypothalamus: arcuate NPY cells drive feeding, while arcuate POMC neurons inhibit feeding
2. In the fasting state, arcuate NPY neurons
   encourage feeding
   a) These are neurons in the arcuate nucleus of the hypothalamus which release neuropeptide Y (NPY), GABA, and (in the case of some cells) also agouti-related peptide (AgRP)
   3.Arc-NPY projects mainly to other hypothalamic areas
   a) Signals from Arc-NPY cells inhibit neurons in the paraventricular nucleus of the hypothalamus (PVN), a satiety or anorexigenic center, i.e. a center that quells your appetite for food.
   b) Arc-NPY signals excite neurons in the lateral hypothalamus (LH), a feeding center.
3. Arc-NPY inhibits PVN’s action on the sympathetic nervous system
   a) High activity in the PVN would excite the sympathetic system, but Arc-NPY inhibits PVN, so the sympathetic system receives very little excitation from there,
   b) i.e. Arc-NPY acts via PVN to decrease sympathetic activity.
4. The result is reduced sympathetic action and therefore more feeding
   a) High sympathetic activity would inhibit feeding, but Arc-NPY inhibits those sympathetic actions, i.e. Arc-NPY disinhibits feeding behavior
5. LH releases orexin, which drives feeding and inhibits PVN
   a) Projections from LH release orexin at their synapses, inhibiting PVN and stimulating feeding behavior, though the mechanisms by which orexin affects feeding are not understood in any detail.

Question 12

1. In the x state, x inhibit feeding
   a) These are another group of neurons in the x, containing not NPY or AgRP but x
   b) They cleave x to make x, which they release at their x
2. Arc-POMC neurons project mainly to x
   a) α-MSH is released from the synapses of x cells and excites neurons in the x and the x
   b) It inhibits neurons in the x
3. One result is increased activity in the x
   a) x and x excite the sympathetic nervous system.
   b) Activity in x inhibits the x, but x inhibits DMH, so the net result is that x, i.e. x
4. x inhibits feeding
5. Arc-POMC is excited by x and inhibited by x

Answer 12

1. In the postprandial state, arcuate POMC neurons inhibit feeding
   a) These are another group of neurons in the arcuate nucleus, containing not NPY or AgRP but pro-opiomelanocortin (POMC).
   b) They cleave POMC to make α-melanocyte stimulating hormone (α-MSH), which they release at their synapses
2. Arc-POMC neurons project mainly to other hypothalamic nuclei
   a) α-MSH is released from the synapses of POMC cells and excites neurons in the PVN and the ventromedial hypothalamus (VMH).
   b) It inhibits neurons in the dorsomedial hypothalamus (DMH
3. One result is increased activity in the sympathetic nervous system
   a) PVN and VMH excite the sympathetic nervous system.
   b) Activity in DMH inhibits the sympathetic system, but Arc-POMC inhibits DMH, so the net result is that sympathetic activity is disinhibited, i.e. increased
4. sympathetic activity inhibits feeding
5. Arc-POMC is excited by sympathetic activity and inhibited by Arc-NPY

Question 13

1. x and x centers receive feedback
   a)Control of feeding, like most control systems in the body, works based on x, i.e. on signals that tell the control center how close the system is to some goal state, or set point.
   b) In feeding, the set point x. Rats with x don’t get fatter and fatter for ever, but level off at a new set point above their original weight; and rats with LH lesions level off at a new, low set point.
2. The hypothalamus infers body weight from **
   a) ** is a protein released into the blood mainly by X, so the more X you have, the more circulating **.
   b) Some cells in the body have X for **, including especially cells in X and X centers of the hypothalamus.
   c) Mutations in the genes that produce ** or the ** receptor
   cause X
3. ** inhibits the feeding centers X and X, and excites X
   A) ** also excites X and X,
   and inhibits X

Answer 13

1. Hypothalamic feeding and anorexigenic centers receive feedback
   a)Control of feeding, like most control systems in the body, works based on negative feedback, i.e. on signals that tell the control center how close the system is to some goal state, or set point.
   b) In feeding, the set point defines a target body weight. Rats with VMH lesions don’t get fatter and fatter for ever, but level off at a new set point above their original weight; and rats with LH lesions level off at a new, low set point.
2. The hypothalamus infers body weight from leptin levels
   a) Leptin is a protein released into the blood mainly by fat cells, so the more fat you have, the more circulating leptin.
   b) Some cells in the body have membrane receptors for leptin, including especially cells in the feeding and anorexigenic centers of
   the hypothalamus.
   c) Mutations in the genes that produce leptin or the leptin receptor
   cause obesity in mice and humans
3. Leptin inhibits the feeding centers Arc-NPY and LH, and excites PVN
   b) Leptin also excites Arc-POMC and VMH,
   and inhibits DMH

Question 14

1. How does your brain know when to end a meal?
   a) Not from leptin, because **: you don’t lay on much new fat during a single meal. The control system needs faster sources of feedback.
   b) One of these faster signals is **:: it **:: as you eat, and its rising level excites **:: and inhibits **::, inhibiting **::
   c) Other mechanisms involve **:: and **:: that measure **:: and **::, and respond by **::that act on the **::
2. In the postprandial state, **::
   inhibit feeding
   a) Sensors in the wall of the small intestine detect **:: and **:: and **::, leading to the release of **:: **::and **::
   b) These hormones act via the **:: to excite **::, **::, and **:: and to inhibit **::. They also excite the **::, which excites **:: via the **::
3. in fasting, **:: released from the stomach encourages **::
   a) **::, the hunger hormone, is released into the blood by **:: when **::; stretching the stomach **::
   b) **:: acts directly on **:: and **:: (exciting them) and on **:: (inhibiting it)

Answer 14

1. How does your brain know when to end a meal?
   a) Not from leptin, because it is too slow: you don’t lay on much new fat during a single meal. The control system needs faster sources of feedback.
   b) One of these faster signals is blood glucose: it increases as you eat, and its rising level excites Arc-POMC and inhibits LH, inhibiting further feeding.
   c) Other mechanisms involve sensors in the walls of the stomach and intestines that measure nutrients and stretch, and respond by releasing hormones that act on the hypothalamus
2. In the postprandial state, gut hormones
   inhibit feeding
   a) Sensors in the wall of the small intestine detect stretch and sugar and protein, leading to the release of cholecystokinin (CCK), peptide YY (PYY), and glucagon-like peptide 1 (GLP-1).
   b) These hormones act via the blood to excite Arc-POMC, PVN, and VMH and to inhibit DMH. They also excite the vagus nerve, which excites VMH via the nucleus tractus solitarius, NTS
3. in fasting, ghrelin released from the stomach encourages feeding
   a) Ghrelin, the hunger hormone, is released into the blood by cells in the stomach wall when the stomach is empty; stretching the stomach stops ghrelin release.
   b) Ghrelin acts directly on Arc-NPY and LH (exciting them) and on PVN (inhibiting it)

Question 15

Drug treatments for obesity

1. Many drugs suppress **, but **,, e.g. amphetamines and fenfluramine (an anti-obesity drug withdrawn in 1997 because of cardiovascular side effects).
2. Rimonabant, which blocks **,, can lead to **,, but causes **,, **,, and **,.
3. **, rarely helps, because **,
4. **, and **, agonists have been tested, without much success. A **, agonist called **, may be better.

Answer 15

1. Many drugs suppress appetite, but they are dangerous, e.g. amphetamines and fenfluramine (an anti-obesity drug withdrawn in 1997 because of cardiovascular side effects).
2. Rimonabant, which blocks CB1 endocannabinoid receptors, can lead to moderate weight loss, but causes nausea, major depression, and suicide.
3. Leptin rarely helps, because fewer than 1% of humans with morbid obesity are leptin-deficient.
4. CCK and PYY agonists have been tested, without much success. A GLP-1 agonist called liraglutide may be better.

Question 16

1. Many living things have circadian rhythms
   a) As the Earth turns, our environment changes X: darker at night, brighter in the day. To adapt, we have X, e.g. we sleep at night, hunt or forage in daylight.
   b) Circadian rhythms are found in X, X, X, X, and X.
   c) Humans have circadian rhythms of X, X, X, X and X
2. Circadian rhythms are X
   a)They are not simply x ; rather, they continue even when X, e.g. plants open and close their leaves on a 24-hour cycle even when light and temperature are constant.
   b) Almost every cell in your body has X that oscillates on X, though these clocks can be
   X by X acting through a master clock in your X

Answer 16

1. Many living things have circadian rhythms
   a) As the Earth turns, our environment changes on a 24-hour cycle: darker at night, brighter in the day. To adapt, we have evolved circadian (roughly 24-hour) rhythms of physiology and behavior, e.g. we sleep at night, hunt or forage in daylight.
   b) Circadian rhythms are found in bacteria, protozoa, plants, fungi, and animals.
   c) Humans have circadian rhythms of behavior, alertness, mood, body temperature, and hormone levels
2. Circadian rhythms are endogenous
   a)They are not simply responses to changes in the environment; rather, they continue even when the environment is held constant, e.g. plants open and close their leaves on a 24-hour cycle even when
   light and temperature are constant.
   b) Almost every cell in your body has its own internal clock that oscillates on a roughly 24-hour schedule, though these clocks can be
   entrained (i.e. kept in sync) by sensory signals acting through a master clock in your brain

Question 17

1. Studies in fruit flies have revealed a gene involved in circadian rhythms
   a) A gene called **, or **,, on the **,, shows **, — it is transcribed when , so its mRNA is most abundant around **,. Its protein product, **,, is most abundant **, hours later.
   b) PER (with other factors) represses **, (and in the absence of PER, **,, i.e. PER and its mRNA **,, in a **,
2. Another gene called **, or **,
   is also crucial
   a) Other studies in fruit flies have shown that tim mRNA and its protein product, **,, oscillate much like **,
   b) TIM binds **,, and it is the dimer **, that **,.
   c) This self-repression drives a cycle. Around 4 a.m., **, shut off per and tim, so **,. So per and tim, **, in late evening, leading to a **, next morning at **, a.m.
   d) If either TIM or PER is absent, **,
3. So these proteins oscillate in a roughly
   **, rhythm
4. PER/TIM acts by blocking **,
   a) A gene called **, (or **,) codes a protein **,, and a gene called **, (or **,) codes **,. In the daytime, the dimer **, binds DNA and stimulates **,
   b) In the night, **, blocks **,, and so represses **,

Answer 17

1. Studies in fruit flies have revealed a gene involved in circadian rhythms
   a) A gene called period, or per, on the X-chromosome, shows a 24-hour cycle — it is transcribed mostly early in the night, so its mRNA is most abundant around 10 p.m. Its protein product, PER, is most abundant 6 hours later.
   b) PER (with other factors) represses transcription of per (and in the absence of PER, mRNA levels do not cycle), i.e. PER and its mRNA drive each other’s cycling, in a transcription-translation feedback loop, or TTFL
2. Another gene called timeless or tim
   is also crucial
   a) Other studies in fruit flies have shown that tim mRNA and its protein product, TIM, oscillate much like per mRNA and PER.
   b) TIM binds PER, and it is the dimer PER/TIM that represses transcription of tim and per.
   c) This self-repression drives a cycle. Around 4 a.m., high levels of PER/TIM shut off per and tim, so PER/TIM levels gradually fall. So per and tim, no longer repressed, rise to a peak in late evening, leading to another peak in PER/TIM next morning at 4 a.m.
   d) If either TIM or PER is absent, neither one oscillates
3. So these proteins oscillate in a roughly
   24-hour rhythm
4. PER/TIM acts by blocking positive transcription factors
   a) A gene called clock (or clk) codes a protein CLK, and a gene called cycle (or cyc) codes CYC. In the daytime, the dimer CLK-CYC binds DNA and stimulates transcription of per and tim.
   b) In the night, PER/TIM blocks CLK-CYC binding to DNA, and so represses transcription of per and tim

Question 18

1. A gene called ** or ** lengthens the cycle
   a) Translation is a ** process, and so we might expect **, which would
   result **
   b) But the protein DBT binds **, causing i, so ** resulting in an overall cycle length near 24 hours
2. The human system is less well understood, but **
   a) Mammals have ** of ** that play a similar role, though mammalian PER ** not with TIM but with a protein called **, from the ** gene. Mammals have homologs of tim, but **
   b) Mammalian homologs of clk, cyc, and dbt are called **, **, and **.
   c) In mice and likely other mammals, a ** stimulates transcription of ** and ** when not blocked by **. ** slows the rise of PER protein levels

Answer 18

1. A gene called doubletime or dbt lengthens the cycle
   a) Translation is a quick process, and so we might expect PER and TIM levels to lag per and tim by only a short interval, which would
   result in a cycle much shorter than 24 hours.
   b) But the protein DBT binds PER, causing it to break down, so levels of PER rise much more slowly than they otherwise would, and so they do not peak until 6 hours after per, resulting in an overall cycle length
   near 24 hours
2. The human system is less well understood, but uses a similar TTFL
   a) Mammals have homologs of per that play a similar role, though mammalian PER forms a dimer not with TIM but with a protein called CRY, from the cryptochrome or cry gene. Mammals have homologs of tim, but their functions are unclear.
   b) Mammalian homologs of clk, cyc, and dbt are called clk, bmal1, and ck1ε.
   c) In mice and likely other mammals, a CLK/BMAL1 dimer stimulates transcription of per and cry when not blocked by PER/CRY. CK1ε slows the rise of PER protein levels

Question 19

1. How are the cellular clocks kept in sync?
   a) With a clock in X, the human body is like a clock shop with X trillion clocks. If they were left to run independently, X
   b) But they are kept in sync by X, e.g. X, X, X, X, and X; all such cues are called **.
   c) The main ** is X sensed by X, which project to the master clock: X of the X.

Answer 19

1. How are the cellular clocks kept in sync?
   a) With a clock in almost every cell, the human body is like a clock shop with 10 trillion clocks. If they were left to run independently, they would come out of sync with each other and with the external rhythm of night and day.
   b) But they are kept in sync by several external factors, e.g. light, temperature, feeding, exercise, and social interaction; all such cues are called zeitgeber.
   c) The main zeitgeber is light sensed by melanopsin retinal ganglion cells, which project to the master clock: the suprachiasmatic nucleus (SCN) of the hypothalamus.

Question 20

1. The SCN sits **
2. The cellular clocks in the SCN are reset by **
   a) Signals from ** reach certain neurons in the SCN, making them **and **
   b) i.e. the retinal signals cause ** that lead to **
   c) if this drop in **occurs after ~ 4 a.m., when **, then it **; if it happens in the evening, when **, it **
3. An example: light at 6 a.m. **
   a) Here, a half-hour of light from 6‒6:30 a.m. **, i.e. the clock is now **
4. From the SCN, information about l** spreads throughout the body
   a) The SCN neurons that ** send signals onward to other neurons in the SCN, so their **
   b) From there, neural signals pass to ** which in turn **
   c) This process of nudging a clock into synchrony with another rhythm is called **. So the SCN becomes ** to **, and other clocks are ** to the ** and through it to **

Answer 20

1. The SCN sits above the optic chiasm
2. The cellular clocks in the SCN are reset by light
   a) Signals from melanopsin retinal ganglion cells reach certain neurons in the SCN, making them fire and resetting their clocks by a small amount,
   b) i.e. the retinal signals cause chemical changes in these SCN cells that lead to a breakdown of PER/CRY;
   c) if this drop in PER/CRY occurs after ~ 4 a.m., when PER/CRY levels are already falling, then it sets the clock forward a little; if it happens in the evening, when PER/CRY levels are rising, it sets the clock back
3. An example: light at 6 a.m. sets the clock forward
   a) Here, a half-hour of light from 6‒6:30 a.m. accelerates the break- down of PER/CRY, reducing it to a level it would otherwise have
   reached a little later, i.e. the clock is now running a little ahead.
4. From the SCN, information about light and dark spreads throughout the body
   a) The SCN neurons that receive retinal projections send signals onward to other neurons in the SCN, so their intracellular clocks are adjusted as well.
   b) From there, neural signals pass to other brain areas, which in turn send neural and hormonal signals that adjust the intracellular clocks throughout the body.
   c) This process of nudging a clock into synchrony with another rhythm is called entrainment. So the SCN becomes entrained to night and day, and other clocks are entrained to the SCN and through it to
   night and day.

Question 21

1. In darkness, the pineal body releases **
   a) SCN neurons project, via other ** and then the **, to the **, at the **
   b) The pineal secretes the **, more in **, less in **. Starting at dusk, **, peaking at ** a.m., and then fall back to ** by ** a.m.
   c) Melatonin acts via ** in the ** to **
2. The pineal is in the **
3. ** can reduce jet lag
   a) In jet lag, the SCN master clock adjusts itself **, but **.
   b) Melatonin pills can help if they are taken correctly, i.e. for eastward travel, **
   c) People also take melatonin pills to **, but **, e.g. we may fall asleep a few minutes sooner, but sleep duration may not change

Answer 21

1. In darkness, the pineal body releases melatonin
   a) SCN neurons project, via other hypothalamus nuclei and then the sympathetic nervous system, to the pineal body, at the back of the diencephalon.
   b) The pineal secretes the “darkness hormone” melatonin, more in darkness, less in light. Starting at dusk, blood levels rise 8-fold, peaking at 2 a.m., and then fall back to daylight levels by 8 a.m.
   c) Melatonin acts via melatonin receptors in the SCN to reset the master clock toward night time
2. The pineal is in the diencephalon
3. Melatonin pills can reduce jet lag
   a) n jet lag, the SCN master clock adjusts itself gradually to the new schedule of light and dark, but by only one hour per day.
   b) Melatonin pills can help if they are taken correctly, i.e. for eastward travel, 30 minutes before your target bed time at your destination.
   c) People also take melatonin pills to help them sleep, but there is no proven benefit, e.g. we may fall asleep a few minutes sooner, but sleep duration may not change

Question 22

1. Probably all animals sleep, but X
   a) All tested species sleep, including insects and jellyfish.
   b) Diurnal and nocturnal animals sleep at different times, and even within a species there are chronotypes, e.g. X
   c) Chronotypes likely evolved for X
2. Sleepiness depends partly on the X
   a) In daylight, the SCN X neurons in the X so they release X, causing X; loss of X causes X.
   b) In darkness, other cells in the X are active; they project throughout the brain, releasing X and X
   c) X and X inhibit each other
3. Sleepiness also depends on X
   a) While we are awake, breakdown of ATP in the brain causes X. During sleep, X and X.
   b) Caffeine blocks X but does not lower X, so when the caffeine wears off, we “crash”.
   c) Caffeine has a half-life of X: its blood level is halved in X, falls to X in 12 h, to X in 18 h, etc

Answer 22

1. Probably all animals sleep, but not all at the same time
   a) All tested species sleep, including insects and jellyfish.
   b) Diurnal and nocturnal animals sleep at different times, and even within a species there are chronotypes, e.g. human early birds go to bed early and get up early, night owls stay up late and sleep late.
   c) Chronotypes likely evolved for the security of the herd, because they shorten the time when everyone is asleep
2. Sleepiness depends partly on the master clock
   a) In daylight, the SCN indirectly excites neurons in the lateral hypothalamus (LH) so they release orexin, causing arousal; loss of orexin causes narcolepsy.
   b) In darkness, other cells in the LH are active; they project throughout the brain, releasing the neuropeptide melanin-concentrating hormone (MCH) and inducing sleep.
   c) Orexin neurons and MCH neurons inhibit each other
3. Sleepiness also depends on sleep pressure
   a) While we are awake, breakdown of ATP in the brain causes a buildup of adenosine, making us sleepy. During sleep, ATP levels are restored and adenosine levels fall.
   b) Caffeine blocks adenosine receptors but does not lower adenosine levels, so when the caffeine wears off, we “crash”.
   c) Caffeine has a half-life of 6 hours: its blood level is halved in 6 h, falls to 1/4 in 12 h, to 1/8 in 18 h, etc

Question 23

1. There are X stages of sleep
   a) In rapid-eye-movement (REM) sleep, X, you X, you X, and X (so you don’t act out your dreams).
   B) Only birds and mammals have REM sleep, and aquatic mammals such as dolphins lack it, likely because without muscle tone they
   would drown; seals have REM sleep on land but not in the water.
2. The stages follow each other in a X
   a) The first REM stage occurs after X. As the night progresses, X
3. You need your sleep for good cognitive function
   a) Deprivation of sleep, or even of just REM sleep, causes problems with X, X, and X.
   b) After sleep deprivation, your first sleep will catch up on X, but the next few nights will have X
   c) Humans sleep X than other primates, but with more X, and on the ground rather than up a tree.

Answer 23

1. There are 4 stages of sleep
   a) In rapid-eye-movement (REM) sleep, your eyes move, you dream, you have erratic 30‒40 Hz brain waves (as in wakefulness), and your muscle tone vanishes (so you don’t act out your dreams).
   B) Only birds and mammals have REM sleep, and aquatic mammals such as dolphins lack it, likely because without muscle tone they
   would drown; seals have REM sleep on land but not in the water.
2. The stages follow each other in a 90-minute cycle
   a) The first REM stage occurs after about 90 minutes. As the night progresses, sleep gets shallower and REM stages longer, and you
   may wake up occasionally
3. You need your sleep for good cognitive function
   a) Deprivation of sleep, or even of just REM sleep, causes problems with cognitive function, learning, and memory.
   b) After sleep deprivation, your first sleep will catch up on NREM, but the next few nights will have more REM than usual.
   c) Humans sleep less than other primates, but with more REM, and on the ground rather than up a tree.