Lecture 5- How do Clock Cells Talk Flashcards
What indicates that the SCN depends on intracellular communication
The fact that the SCN contains synchronised high amplitude rhythms and desynchronised low amplitude rhythms
AVP (vasopressin)
location of receptor expression
location of AVP neurons within the SCN
V1a and V1b are expressed in the SCN, with AVP neurons being more prevalent along the medial aspect of the SCN (in shell)
What kind of receptors are neuropeptide receptors?
GPCRs
Mice lacking in V1a and V1b receptors are
resistant to jet lag; can re-entrain much better than WT; rapidly phase shift w changes in LD; do not show transient re-entrainment
IN AVP receptor KO mice, PER gene expression
is reset ~half the time of WT
Clock gene expression in both liver and SCN of V1a/b KOs mice
phase shift rapidly with LD changes i
AVP receptor mice KO considerations
could be because these mice have developed without these key receptors, however pharmacological blockade mimics AVP KO effects making this unlikely
AVP signalling (via V1a and V1b receptors) on the circadian system
ordinarily act as an intrinsic brake on the circadian system to control the rate of re-entrainment, interneural signalling between cells of the SCN normally acts to resist external perturbation on the clock
Jet lag
recovery is about 1 hour per day, harder for the clock to go phase advance than it is delay
VIP (expression)
is abundant in the SCN near OX
VPAC2
also heavily expressed in the SCN
VIP-VPAC2 signalling
has been implicated in the photic entrainment of the SCN via RHT
VIPR2 KO mice
have significantly disrupted wheel running behaviours and almost completely non-existent phasic firing w zeitgeber time, and have a disorganised molecular clock
Pharmacological blockade of VIPR2
prevents peaking in firing rate rhythm (but rhythms are rescued as antagonist washes out)
In the absence of VIP-VPR2 signalling
both amplitude and synchrony are impaired in SCN neurons
VIP and VIPR2 KO mice
are behaviourally arrhythmic, or express accelerated behavioural rhythms
In vitro, VIPR2 KO neurons
show dampened firing and appear arrhythmic
VIPR2 SCN cannot
gate the actions of light on the P-ERK pathway
Insect correlate of VIP
PDF is analogous to
PDH, but lacks a chromatophore
PDF is found in
SLNvs and LLNvs
PDF signalling takes place via
the PDFR receptor, a B1 class GPCR, +vely coupled to adenylate cyclase
PDF KO flies
show disrupted circadian rhythms, lacking morning anticipation and advancement in evening anticipation
PDF and PDFR mutants also show
a marked decrease in rhythm amplitude in DD or may even be arryhthmic
