Exam 4

environment (i.e. day and night) optimal times for behavior vary, but there’s a general pattern behaviors cycle in oscillatory pattern

• Put animal in constant environment (temp, noise, light) • example: constant darkness (DD) • Measure activity (wheel running) • Results: every day, activity starts a little sooner (cycles, but slightly less than 24 hours) • Activity is circadian (periodic) but not exactly 24 hours

circadium rhythm slightly longer than 24 hours (but there’s genetic variation) those w/ most genetic variation likely to have sleep disorders

rhythm of more than 24 hours (unlike less than 24 hours in constant darkness) causes more health problems than in dark since nocturnal

• Found in all organisms • Period in constant conditions is close to, but not exactly 24 hours • Can depend on light dark cycle and other cues (zeitgebers) • Many single cells can display circadian rhythm; multiple cells release hormones to synchronize

nocturnal: sleep during day (mice) diurnal: sleep at night (humans) crepuscular: sleep middle of day and middle of night, active dawn and dusk (fruit flies)

Hall, Rosbash, Young

identified gene that when mutated, change cycle duration called period (per mutants)

discovered the function of the per gene

determined function of a second clock gene, called timeless (tim) found that per and tim proteins bind to each other

• per mRNA levels vary in cyclic fashion • mRNA cycling is circadian (cycle b/w high mRNA and protein levels) • per protein levels are also cyclic, peak level reached several hours after mRNA peak

• Transcribe per mRNA • make per protein in cytosol • import per protein into nucleus • Per protein inhibits its own promoter (mRNA and protein levels fall) • Inhibition is relieved, begin making per mRNA again

proteins clock (dCLK) and cycle (CYC) are required to activate transcription of per and tim per and tim proteins dimerize, are phosphorylated, then enter the nucleus phosphorylated dimer inhibits transcription of per and tim mRNA

via phosphorylation of per and tim proteins by Doubletime (per) and crytochrome genes (tim)

produces kinase that regulates per protein in cytosol degrades per: extends cycle duration by preventing dimer formation

produces kinases that regulate tim proteins in both cytosol and nucleus degrading tim in cytosol: extends cycle duration by preventing dimer formation degrading tim in nucleus: destroys dimer, removing inhibition, next cycle starts

in flies (not mammals): cryptochrome is light sensing protein light activated cryptochrome promotes rapid degradation of tim protein in cytosol (can’t form dimer, cycle stops)

normally: light during day breaks down cytosolic tim, extends cycle duration travel: light during night breaks down nuclear tim, advancing onset of next cycle (shortens cycle duration, phase advance)

there are proteins homologous in structure/function to dCLK, CYC, and PER PER forms dimer with CRY, not TIM (timeless lost) cryptochrome (CRY) not light sensing

CRY isn’t light sensitive light input based on retinal projections to the SCN (suprachiasmatic nucleus)

• isolated SCN cells are sufficient to generate circadian rhythms • electrical synapses b/w SCN neurons synchronizes entire nucleus • intact SCN is necessary for whole animal rhythms • hamsters w/o SCN have no circadian rhythm • when transplant SCN back in, circadian rhythm comes back

melatonin (hormone) gives feedback to SCN melatonin can phase shift SCN clock depending on when it’s present

autonomic innervation body temperature glucocorticoids feeding

drosophila also use hormones to synchronize brain to body, but NOT same hormones as mammals