SCN Flashcards
Evans (2016)
SCN = master clock. Self-sustained rhythms generated by 24h transcriptional-translational feedback loop (clock genes - molecular level). Coordinate rhythms in physiology and behaviour. Synced at tissue level via intercellular signalling (VIP).
Antle (2009)
Only some SCN endogenously rhythmic - intercellular signalling with neuropeptides e.g. NPY, also GABA. Possible pharmacological targets for circadian / sleep dysfunction?
Herzog 1997
SCN cells still generate rhythms when isolated
Prosser 2007
PK2 important signalling factor: syncs core SCN cells to shell. Peaks in day and suppresses locomotor activity in mice
SCN outputs
Other hypothalamic areas e.g. aVPN (melatonin release from pineal, CRH release), subventricular zone, DM nucleus, medial preoptic nucleus (GnRH)
DeCoursey 1989
SCN ablation and transplant of foetal tissue
DeCoursey 2000
Chipmunks
Lucas 2001
Blind people still entrain due to melanopsin RGCs
Hattar 2002
melanopsin tau:lacZ mouse and retrograde staining from SCN - down RHT to retina (1/100 RGCs)
Lucas 2003
Melanopsin RGCs intrinsically photoreceptive, emit APs in vitro. But cells from melanopsin K/O mice don’t show this
Melyan 2005
Put melanopsin into non-photoreceptive cell = becomes photoreceptive
Cholera toxin labelling
Stain RHT input to SCN: see tracts synapse in ventral pattern
Electromicrographs
Postsynaptic densities (RHT synapses) are Gray type I excitatory cells
PACAP immunostaining
Ventral pattern of PACAP staining in SCN: closely matches that of RHT innervation
Khalsa 2003
Similar pattern of PRC seen in humans e.g. light early in night = phase delay
van del pol 1998
Brief pulses (rather than continuous) of light = integrate and can cause even larger phase shifts
Piggins and Guilding 2011
Photic and non-photic stimuli = differential PRCs
Marston 2008
Rodents and arousal-promoting stimuli e.g. dark pulse late in subjective day = phase advance. 6h dark promotes arousal = less cFos expressed in SCN, higher activity in orexin neurons
Harmar 2002
VPAC2R K/O mice = arrythmic in constant dark, no sync of SCN cells. Amp and synchrony of SCN cells impaired - need VIP signalling to synchronise
Hughes 2015
VIP K/O mice in constant light = improved behavioural rhythms so shows light is crucial
Yamaguchi 2013
AVPR K/O mice = resistant to jet lag. Entrain/phase shift much more rapidly, behavioural and molecular (clock gene expression)
Mieda 2015
Also resistant to jet lag if no BMAL in AVP neurons. AVP tries to keep intact clock by resisting large changes in rhythm
Piggins and Guilding 2011
Action of NTs e.g. Glu and PACAP activate VIP receptors in SCN to impact clock gene expression and set/reset phase
Davis 2001
Higher breast cancer rates in night shift workers (constantly phase shifting / clock out of sync). Circadian dysfunction can lead to disease
van Someren 1997
BLT in care homes increases amp of circadian rhythms / improved entrainment (also helps with cognitive problems)
Lewy
Phase delay hypothesis for SAD
Murray 2003
Association between lowered/depressed mood in winter and winter phase delay
Mistlberger 2005
Opponent-process model.
Lesion SCN = homeostatic only, short bouts of sleep/wake.
Ignore sleep homeostat e.g. sleep deprivation = more tired in first night than third day
Forced desynchrony - 28h day. Homeostasis always kept same but measured temp as output of circ clock = 24.3h, freerunning
VLPO
Light info travels down RHT to VLPO, forms excitatory synapses (can be seen with melanopsin tau:lacZ staining).
VLPO is sleep-promoting (GABAergic neurons that switch off ARAS) so in mice = active during day (higher cFos expression). Lesion VLPO = disrupted sleep.
Roenneberg 2009
Chronotype: preferred phase of sleep/wake. Males later, changes with age etc. Social schedule interferes considerably with sleep/activity times so should try and change work/school schedules to suit chronotype!
Social jet lag = wake up too early on weekdays, sleep deprived. Worse in young adults.
Circadian clock controls sleep but according to solar cycle not social schedule!
LeGates 2014
Irregular light linked with depression.
