narcolepsy

what is narcolepsy

disorder of sleep organization

how long do humans sleep

1/3

can total sleep deprivation be fatal

yes

what does sleep loss do to function

impairs it → decreased motor performance

what is sleep

a complex state regulating mobility, arousal, metabolism, and physiology/neurophysiology

tobler sleep criteria

extended immobility, higher arousal threshold, homeostatically regulated, circadian regulation, electrophysiological correlates

mammalian sleep stages

electrophysiological correlates of sleep in mammals

what happens in the first hour of sleep

SWS

what happens after SWS

REM

what happens over sleep period

more SWS early and more REM near the end

what is the two process model for sleep

a theoretical framework for understanding sleep consolidation

process s - what is sleep load

accumulate sleep need

process s - how does sleep load dissipate

with sleep

process s - what does the sleep homeostat do

keep sleep load within a range → upper limit initiate sleep + lower limit wake up

hypothesis process s

sleep homeostat monitors sleep load through the levels of a metabolite

what is a candidate of sleep load

adenosine

what does adenosine promote

sleep

levels of adenosine during wakefulnes

rise

levels of adenosine during ATP breakdown

increase

where are adenosine receptors

in brain sleep regions

example adenosine receptor antagonist

caffeine!

hypothesis of adenosine

promotes wake by blocking sleep load signal

process c - circadian

sleep is consolidated into daily blocks by circadian clock

process c - variability of thresholds

sleep and wake vary across the day

process c - hypothesis

alerting signal during wake that raises the threshold for sleep and makes waking more likely during the day

where do circadian rhythms orginate from

the SCN

how long does the cycle last in core molecular feedback loop

24 hours

symptoms of narcolepsy

excessive daytime sleepiness, fragmented sleep, fast transition to REM from wake

symptoms when rem and wake mix

sleep paralysis, hypnagogic hallucinations, automatic behaviors, cataplexy (type 1)

what is sleep paralysis

conscious, unable to move at sleep wake transitions

what is hypnagogic hallucinations

hallucinations at sleep wake transitions

what is cataplexy

sudden loss of muscle tone that causes feelings of weakness nad loss of voluntary muscle control

when does narcolpesy typically appear

young adulthood + rapid

odds in people

3-5 in 10,000

familial percentage

1-2%, mostly sporadic

odds in monozygotic twins (out of 20)

only 5-7

what is necessary for narcolepsy

environment

what is the human leukocyte antigen in more than 90% narcolepsy cases

DQB1*0602

what do dogs lack that causes narcolepsy

receptor hypocretin/orexin

what is orexin

a neuropeptide that regualtes arousal and appetite

what happens to orexin in humans

distupted!!!! → none in type 1, reduced in type 2

what does human brain tissue with narcolepsy show

fewer hypocretin expressing neurons

channelrhodopsin in mice experiments

experimental tool to manipulate neural activity → light gated channel that depolarizes. stimulation of orexin neurons is sufficient for wake

arousal and sleep circuitry in mammals

mutually inhibitory → keeps wake and sleep separate

where are wake promoting circuits

posterior hypothalamus

regions in wake promoting

raphe nuclei, tuberomammillary nucleus, locus coeruleus

where are sleep promoting circuits

anterior hypothalamus

regions in hypothalamus

ventrolateral preoptic nucleus

what do healthy orexin neurons do

excite brain wake circuitry

orexin neurons in posterior lateral hypothalamus do what

synaptocally activate orexin recepotrs on posterior hypothalamic neurons that promote wake

what happens to sleep centers when wake center is active

inhibited

what happens in narcolepsy bc of orexin neuron loss

disinhibits sleep

flip flop model

orexin neurons excite wake centers and adenosine sleep load signal excites sleep centers

what regulates orexin neurons

SCN, energy balance, limbic sustems

sleep wake mutual inhibition

ensires alternating → will nebver be both sleep and wake

sleep is consolidated into

blocks but needs orexin

what happens to the flip flop since orexin is not present

unstable switching

autoimmune attack - DQB1*0602

may cause loss of orexin neurons bc of the antigen → needs a trigger

vaccines and narcolepsy

pandemrix vaccine → autoimmune response in susceptibke people