Biological rhythms

EEG (electroencephalogram)

•  pooled potential waves recorded from head. •  Vs. "evoked potential," evoked by stimulus. •  To get regular waves, there must be some

synchrony in neuron firing. •  Thalamus to cortex loop may contribute. •  Reticular formation involved in arousal (reticular

activating system) (RAS) may also contribute.

REM

•  Landmark paper •  Aserinsky & Kleitman, •  Regularly occurring periods of eye motility,

and concomitant phenomena, during sleep, Science 118, 273-274, 1953

Sleeping vs awake

•  The relaxed EEG with eyes closed is 8-13 cycles per second (Hz), called alpha (not shown)

•  During arousal there is alpha-blocking, and with eyes open, 14-60 Hz (beta) makes it almost as if there were no rhythm.

REM & non REM sleep •  stages of non REM sleep, defined by EEG. •  stage 4 - Deep sleep - slow wave sleep- delta (and

theta) rhythm •  stage 3, 2 Hz •  REM is associated with dreaming. •  atonia (lack of muscle control) •  PGO spikes at onset of REM •  (pontine RF-> geniculate -> occipital cortex). •  Birds do not have REM sleep but most mammals

do.

States of sleep •  During a night of sleep, go back and forth •  REM - heart rate, respiration, erection all increase. •  Called "paradoxical sleep" because it seems like

awake state. •  Deprivation of paradoxical sleep makes a person

or animal irritable. •  Because of loss of muscle tone, a cat restrained

over a dish of water will wake up when it goes into REM sleep.

Jouvet, 1967, 1969, papers

•  Hobson - raphe & l. coeruleus off in sleep. •  involvement of several neurotransmitters •  1960's Dahlstrom, Fuxe) histochemical

fluorescence in which 5-HT, NE and DA pathways could be visualized since the products of transmitter reacted with paraformaldehyde vapor can be seen.

•  Ascending reticular activating system: •  (1) Raphe (ridge or seam) nuclei uses 5-HT •  caudal innervates downward, rostral upward. •  fires during wakefulness, involved in sleep. •  hallucinogenic LSD lysergic acid diethylamide •  agonist of presynaptic raphe 5-HT receptors •  inhibits firing (like in sleep), •  peyote (cactus) Aztec, psilocybin (mushroom)

Maya

more

•  (2) locus coeruleus (blue spot), •  bilateral in the pons, •  spreads NE around brain. •  12,000 neurons (each) 250,000 synapses. •  Like sympathetic ganglion in brain- •  activated by sensory stimulation •  (3)The pontomesocephalotegmental complex

regulates thalamic sensory relays using acetylcholine.

Transmitter relations •  other Ach systems: •  septal area (->hippocampus) •  basal nucleus of Meynert (->neocortex) •  [these cells die early in Alzheimer's disease] •  dopamine nigrostriatal Parkinson's •  mesocorticolimbic (reward) system •  tegmentum to forebrain and limbic system. •  Cocaine blocks DA reuptake, amphetamine blocks

NE & DA reuptake, potentiating reward •  Depletion by alpha-methyl-para-tyrosine blocks

stimulant action.

Circuits

5HT & NE -> -> Glycine to spinal motor neuron to inhibit motor movement.

GABA to dorsal column nuclei to inhibit sensation.

Biological clocks

•  There are many rhythms in people, •  3/min Parkinson tremors, •  the 21 day cycle in manic-depression, •  the 28 day human menstrual cycle, •  circannual (about a year), •  ultradian (fast, less than a day).

Jargon, etc

•  photophase, scotophase, free-run, endogenous

•  Entrainment, zeitgeber (time giver) •  biological rhythms, periodicity, biological

clocks •  circadian (about a day) •  Note human volunteer goes to >24 hr.

Ashoff’s rule

•  light on - nocturnal increase period •  - like waiting for night •  light off - diurnal increase period •  - like waiting for day

Landmark Menaker, 1972,

•  What is the photoreceptor? •  (extraretinal in sparrows and fruitflies)? •  Where is the clock? (different question) •  pineal small heads lizards. •  Light may even hit the pineal in birds, •  enucleated sparrows India ink under skin in

head to decrease light and feather plucking to increase light

Pineal, reproduction

•  In seasonally reproductive birds, testes size in affected by more light in reproductive season.

•  The pineal has photoreceptors, rhodopsin and molecules of the phototransduction cascade.

Recent Paper

•  Panda et al., Melanopsin is required for non-image-forming photic responses in blind mice,

•  Pigment may be a different opsin (melanopsin [expressed in melanophores]) (and may be in ganglion cells).

In the brain

•  suprachiasmatic nucleus is important - •  lesions in SCN disrupt rhythm. •  There is a mutant (named "tau") in the

hamster affecting the SCN with altered rhythm.

Drosophila •  locomotory rhythm and rhythm of pupal

emergence. •  Some classic work •  Action spectrum for entrainment drops off

dramatically above 500 nm. •  Deprivation of carotenoids does not decrease

sensitivity for entrainment. •  Suggests that the photoreceptive pigment is not

rhodopsin.

"genetic dissection"

•  Seymour Benzer at Caltech •  with Ron Konopka, found "period" gene. •  per=period, l=long, s=short, 0=arythmic, •  perl 29 hr, pers 19 hr, per0 - fast rhythm(?) •  Clock or photoreceptor localized to brain. •  rhythm in courtship song, an ultradian rhythm, •  affected by per. •  PER is a nuclear protein whose mRNA and

protein cycle.

Recent paper •  Busza et al., Drosophila CRYPTOCHROME

Structural domains 2004. •  Cryptochrome is blue sensitive protein (relates to

points above about the pigment not using carotenoids and being short wavelength sensitive).

•  PERIOD and TIMELESS dimerize and act as negative transctiption factor.

•  Interfere with action of CLOCK and CYCLE. •  CRY binds to TIM, and they are degraded by

proteasome.