Biological Rhythms:

n Regular, periodic cycles of physiological/psychological functioning

n Most common: circadian rhythms: ~24 hr cycles in many biological processes & behaviors

n Also biorhythms of other lengths (yearly, monthly, etc.)

n Rhythms are endogenous (generated internally, by biological clocks) but are influenced or “reset” by external stimuli.

Picture of Cyclic Changes in Alertness, Temperature, Growth Hormone, Cortisol

Biorhythms continued...

n Even if deprived of time of day signals, our biorhythms run on their own internal clock: “free-running rhythms” often with a cycle of slightly over 24 hr (average = 24.2)

n Daylight is key external “zeitgeber”, resetting our biological clock & keeping it “entrained” with the cycle of where we are living. Other less effective zeitgebers: exercise/activity, temperature, noise, meals.

n Retinal blindness can disturb this resetting (some blind individuals have free-running rhythms), but the internal clock itself is very resistant to disruption.

Picture of the “Free-Running” Sleep Cycle of an individual kept isolated from all time of day cues. They continue to sleep the same number of hours every night despite the lack of cues. But because the natural rhythm of their biological clock is slightly longer than 24 hours, their sleep period begins a little later each successive day, so that after 7 days they go to bed at 4 am and after 2 weeks they go to bed at 10 am.

Biological Clocks

n Key internal clock: suprachiasmatic nuclei (SCN) of the hypothalamus (~10,000 neurons)

n SCN lesions disrupt activity, sleep, eating, & hormone rhythms.

n SCN shows rhythmic firing activity even when isolated from rest of brain.

n SCN transplants can change an animal’s natural biorhythm to that of donor.

n SCNs receive direct input from eyes & are active during daylight hours, but also evidence light from other parts of body may play a role too!

Picture of the location of the SCN in the hypothalamus immediately above the optic chiasm (point where the 2 optic nerves join together)

Graph of the circadian changes in the rate of firing of isolated SCN neurons

Figure showing very regular circadian shifts in rat’s activity cycles before surgery (top) and total loss of the normal sleep/waking cycle after (bottom) SCN lesions

Suprachiasmatic Nucleus (SCN) diagram also showing the location of the pineal gland dorsal to the midbrain, close to the superior colliculi

Researchers, studying other species, have discovered 3

rhythm related genes which trigger daily production of proteins which accumulate over the day & make you sleepy.

Light increases protein production; production stops during night. Problems with these genes are associated with abnormalities in sleep cycle.

Bad “clock” gene – sleep less

Bad “period” gene – sleep & wake too early

Too much night light – decreases activity of “timeless” gene, don’t get sleepy at right time.

Melatonin

n SCN regulates pineal gland production of melatonin. Melatonin is produced mainly at night, beginning about 2-3 hrs before our bedtime.

n Makes you sleepy within ~2-3 hrs

n Melatonin (~.3mg) in the afternoon may make you sleepy earlier; melatonin after midnight may help you adjust to sleeping later.

n SCN has melatonin receptors (probably allows feedback)

n SCN control of rhythms shows some deterioration with aging

Desynchronization of work cycle and circadian cycles causes accidents

Graph of number of single vehicle truck accidents by hour of day – looks like a “circadian rhythm of accidents” with few single vehicle accidents during daytime hours (1% of the accidents occurring at each of the daytime hours except lunchtime- a few more then) and a huge increase during nighttime hours when drivers are fighting their natural biorhythms. During the night hours – as early as 11 PM incidence has risen to 7% of accidents occurring then, by 1 am 11% of accidents occur then and by 5 am 19% of the accidents occur at that hour.

Shifting Your Biorhythms

n You must control your environment to provide the right cues to your SCN

n For several days before your shift:

u Expose yourself to bright light beginning at the time of your “new morning”

u Dim or no lights at time of new “night-time”

u Match mealtimes, exercise times to new cycle

u Maintain exposure to “correct” stimuli to keep new biorhythms entrained

n It is easier to delay your clock (go to bed later, wake up later) than it is to advance your clock (go to sleep earlier, wake up earlier).

Graph of how long it takes to recover from jet-lag and re-establish biorhythms when traveling east (advancing cycle takes ~8 days on average but some take up to 18 days) vs west (delaying your cycle averages 4 days, with a few people taking 8 days).

Polysomnogram

n EEG (electroencephalogram)

n EOG (electrooculogram)

n EMG (electromyogram)

n Sometimes additional measures like respiration, BP, etc.

2 Main Types of Sleep

n Non-REM (about 80% of night)

n REM sleep (20% of night)

Non-REM Sleep (Stages 1-4)

n gradual decrease in movements, breathing, heart rate

n change in brain activity to high voltage slow, rhythmical brain waves (“delta waves”)

n hard to wake up

n sleep-thinking more common than dreaming

REM Sleep

n very active low voltage, fast irregular brain waves similar to waking

n rapid jerky eye movements

n total loss of tone in most muscles

n breathing, heart rate unpredictable

n 80-90% chance of vivid dream report

n erection; vaginal lubrication

Figure of typical appearance of EEG tracings during different stages

Low voltage irregular beta waves during alertness

More rhythmical alpha waves during relaxation

Even larger, slower more rhythmical brain waves during each of the successively deeper stages of NREM or “slow wave” sleep

Graph of the cyclical changes in sleep stage throughout the night

Anatomy of Sleep Classics

n Bremer’s passive, sensory theory of sleep and his cerveau isole (cut through midbrain isolating forebrain) & encephale isole surgeries

n Damage and stimulation studies of the reticular formation (Lindsey; Moruzzi & Magoun)

n Jouvet – raphe lesions in catsà insomnia

n Now we know there are multiple brainstem and basal forebrain circuits related to different components of sleep & waking

Diagram of where Bremer made cuts through the brain - Cerveau Isole` versus Encephale Isole’

Diagram of Reticular Activating System

Other “Arousal” Areas

n Locus coeruleus of pons sends arousing NE messages throughout forebrain during waking, especially whenever something important/emotional happens. NE seems to strengthen the memories of that event.

n Basal forebrain (nucleus basalis) – ACh neurons to all of cortex

n Hypothalamus histamine neurons

Sleep Circuits Involve Basal Forebrain & Brainstem Areas (complex interconnected sleep/waking system)

What happens if something goes wrong in these sleep control circuits?

REM Sleep Behavior Disorder

n Failure of the usual muscle paralysis mechanism of REM so the person can move during dreaming; more frequent in elderly.

Narcolepsy (1/1000 people)

n Persistent daytime sleepiness & irresistible REM sleep attacks (but may not sleep well at night)

n Cataplexy (sudden loss of muscle tone while still awake), often triggered by laughter, anger, embarrassment, sex, exertion, or talking to strangers.

n Sleep paralysis when falling asleep or waking

n Hypnagogic hallucinations (dreams while awake)

n Genetically based in dogs and some humans; may be autoimmune based in those with no affected relatives; only 25% concordance in identical twins.

Narcolepsy continued

n Begins in late teens/twenties

n Associated with some neuron loss in basal forebrain and limbic areas in dogs and abnormality in a recently discovered transmitter (hypocretin/orexin)

n Treated with stimulants, antidepressants & modafinil (Provigil).

Narcoleptic Sleep Attack

Another REM related disorder:

n REM Behavior Disorder – deterioration of cells in pons which normally inhibit muscle tone/movement during REM

n Movements occur during dreaming

n Most common in older men

n Has been experimentally produced in animals by producing brain lesions in this region

NREM Sleep Disorders

n NREM sleep “disorders” are very common in kids and tend to run in families. Most outgrown them. A much smaller # of adults continue to have NREM disorders.

n Sleep-walking

n Night terrors (partial arousal associated with intense anxiety during 1^st few hours of sleep; no memory of it next morning)

Other Sleep Disorders

n Many different causes/types of insomnia, e.g.

u Insomnia caused by drugs

u “Onset” insomnia (trouble falling asleep)(often associated with phase-delayed temp cycle)

u “Termination” insomnia (waking too early) (often associated with phase-advanced temp cycle)

u Depression: termination insomnia & early REM

u Insomnia may also be related to “restless legs” or involuntary movements (PLMD) of legs

u Insomnia due to sleep apnea

Why Do We Sleep?

n Repair/restoration theory: sleep allows the body/brain to repair and replenish itself. We would expect more sleep after more wear and tear on body/brain.

n BUT:

u Length of sleep of species not strongly correlated with activity (including humans).

u Sleep deprivation causes less disruption than expected; we don’t make up for what we miss

u Some individuals routinely sleep only 1-3 hrs, many with only 5 hr..

Evolutionary Theory

n Sleep was “selected for” in the process of evolution - it has survival value beyond restoration of the body. It allows conservation of energy/safety at a time when food-seeking is inefficient or unsafe.

u Sleep time is negatively correlated with exposure/vulnerability during sleep and and also negatively correlated with the time needed to meet energy needs.

u “Biological clock” that triggers periodic changes in arousal independent from need for restoration.

Species Differences in sleep length

Why REM Sleep- Some Proposals

n To provide periodic activation and growth of neurons

u Activation – synthesis theory – dreams are the result of the brain trying to “interpret” this periodic activation

u Clinico-anatomical hypothesis – dreams have their particular qualities because of the particular parts of the brain that are active or suppressed during REM

n To store memories

n To trigger eye movements to oxygenate corneas

Graph of Developmental Changes in Sleep Stages

Circadian Changes in Depression

n Sleep cycle advanced: little SWS, early REM & more REM despite early awakening

n Either REM deprivation or total sleep deprivation can relieve depression

n Antidepressants drugs delay and decrease REM sleep, making it more normal

n Family members (even infants) are also likely to show sleep abnormalities which predict their risk of depression.

Shift Work

Genetics of Circadian Rhythms

n Length of free-running rhythm seems to be genetically determined.

n Recent discovered mutations which abolish rhythms in mice or shorten cycle in hamsters

n Genes also involved in how light influences rhythms - daylight triggers short-term expression of a gene (c-fos)in the SCN, which affects expression of other genes.

Normal Sleep Onset