SCN

Question 1

Evans (2016)

Answer 1

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).

Question 2

Antle (2009)

Answer 2

Only some SCN endogenously rhythmic - intercellular signalling with neuropeptides e.g. NPY, also GABA. Possible pharmacological targets for circadian / sleep dysfunction?

Question 3

Herzog 1997

Answer 3

SCN cells still generate rhythms when isolated

Question 4

Prosser 2007

Answer 4

PK2 important signalling factor: syncs core SCN cells to shell. Peaks in day and suppresses locomotor activity in mice

Question 5

SCN outputs

Answer 5

Other hypothalamic areas e.g. aVPN (melatonin release from pineal, CRH release), subventricular zone, DM nucleus, medial preoptic nucleus (GnRH)

Question 6

DeCoursey 1989

Answer 6

SCN ablation and transplant of foetal tissue

Question 7

DeCoursey 2000

Answer 7

Chipmunks

Question 8

Lucas 2001

Answer 8

Blind people still entrain due to melanopsin RGCs

Question 9

Hattar 2002

Answer 9

melanopsin tau:lacZ mouse and retrograde staining from SCN - down RHT to retina (1/100 RGCs)

Question 10

Lucas 2003

Answer 10

Melanopsin RGCs intrinsically photoreceptive, emit APs in vitro. But cells from melanopsin K/O mice don’t show this

Question 11

Melyan 2005

Answer 11

Put melanopsin into non-photoreceptive cell = becomes photoreceptive

Question 12

Cholera toxin labelling

Answer 12

Stain RHT input to SCN: see tracts synapse in ventral pattern

Question 13

Electromicrographs

Answer 13

Postsynaptic densities (RHT synapses) are Gray type I excitatory cells

Question 14

PACAP immunostaining

Answer 14

Ventral pattern of PACAP staining in SCN: closely matches that of RHT innervation

Question 15

Khalsa 2003

Answer 15

Similar pattern of PRC seen in humans e.g. light early in night = phase delay

Question 16

van del pol 1998

Answer 16

Brief pulses (rather than continuous) of light = integrate and can cause even larger phase shifts

Question 17

Piggins and Guilding 2011

Answer 17

Photic and non-photic stimuli = differential PRCs

Question 18

Marston 2008

Answer 18

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

Question 19

Harmar 2002

Answer 19

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

Question 20

Hughes 2015

Answer 20

VIP K/O mice in constant light = improved behavioural rhythms so shows light is crucial

Question 21

Yamaguchi 2013

Answer 21

AVPR K/O mice = resistant to jet lag. Entrain/phase shift much more rapidly, behavioural and molecular (clock gene expression)

Question 22

Mieda 2015

Answer 22

Also resistant to jet lag if no BMAL in AVP neurons. AVP tries to keep intact clock by resisting large changes in rhythm

Question 23

Piggins and Guilding 2011

Answer 23

Action of NTs e.g. Glu and PACAP activate VIP receptors in SCN to impact clock gene expression and set/reset phase

Question 24

Davis 2001

Answer 24

Higher breast cancer rates in night shift workers (constantly phase shifting / clock out of sync). Circadian dysfunction can lead to disease

Question 25

van Someren 1997

Answer 25

BLT in care homes increases amp of circadian rhythms / improved entrainment (also helps with cognitive problems)

Question 26

Lewy

Answer 26

Phase delay hypothesis for SAD

Question 27

Murray 2003

Answer 27

Association between lowered/depressed mood in winter and winter phase delay

Question 28

Mistlberger 2005

Answer 28

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

Question 29

VLPO

Answer 29

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.

Question 30

Roenneberg 2009

Answer 30

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!

Question 31

LeGates 2014

Answer 31

Irregular light linked with depression.