Aberrant gating of photic input to the suprachiasmatic circadian pacemaker of mice lacking the VPAC2 receptor.
VIP acting via the VPAC(2) receptor is implicated as a key signaling pathway in the maintenance and resetting of the hypothalamic suprachiasmatic nuclei (SCN) circadian pacemaker; circadian rhythms in SCN clock gene expression and wheel-running behavior are abolished in mice lacking the VPAC(2) receptor (Vipr2(-/-)). Here, using immunohistochemical detection of pERK (phosphorylated extracellular signal-regulated kinases 1/2) and c-FOS, we tested whether the gating of photic input to the SCN is maintained in these apparently arrhythmic Vipr2(-/-) mice. Under light/dark and constant darkness, spontaneous expression of pERK and c-FOS in the wild-type mouse SCN was significantly elevated during subjective day compared with subjective night; no diurnal or circadian variation in pERK or c-FOS was detected in the SCN of Vipr2(-/-) mice. In constant darkness, light pulses given during the subjective night but not the subjective day significantly increased expression of pERK and c-FOS in the wild-type SCN. In contrast, light pulses given during both subjective day and subjective night robustly increased expression of pERK and c-FOS in the Vipr2(-/-) mouse SCN. Although photic stimuli activate intracellular pathways within the SCN of Vipr2(-/-) mice, they do not engage the core clock mechanisms. The absence of photic gating, together with the general lack of overt rhythms in circadian output, strongly suggests that the SCN circadian pacemaker is completely dysfunctional in the Vipr2(-/-) mouse.
Hughes
Alun T
AT
School of Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Fahey
Briana
B
Cutler
David J
DJ
Coogan
Andrew N
AN
Piggins
Hugh D
HD
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001683:Biological Clocks / Q000235:genetics / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D003624:Darkness; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009043:Motor Activity / Q000235:genetics / Q000502:physiology; D010775:Photic Stimulation / Q000379:methods; D017440:Photoperiod; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000502:physiology*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000502:physiology*
D016760:Proto-Oncogene Proteins c-fos; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases