Gastrin-releasing peptide promotes suprachiasmatic nuclei cellular rhythmicity in the absence of vasoactive intestinal polypeptide-VPAC2 receptor signaling.
Vasoactive intestinal polypeptide (VIP) and gastrin-releasing peptide (GRP) acting via the VPAC2 receptor and BB2 receptors, respectively, are key signaling pathways in the suprachiasmatic nuclei (SCN) circadian clock. Transgenic mice lacking the VPAC2 receptor (Vipr2(-/-)) display a continuum of disrupted behavioral rhythms with only a minority capable of sustaining predictable cycles of rest and activity. However, electrical or molecular oscillations have not yet been detected in SCN cells from adult Vipr2(-/-) mice. Using a novel electrophysiological recording technique, we found that in brain slices from wild-type and behaviorally rhythmic Vipr2(-/-) mice, the majority of SCN neurons we detected displayed circadian firing patterns with estimated periods similar to the animals' behavior. In contrast, in slices from behaviorally arrhythmic Vipr2(-/-) mice, only a small minority of the observed SCN cells oscillated. Remarkably, exogenous GRP promoted SCN cellular rhythms in Vipr2(-/-) mouse slices, whereas blockade of BB2 receptors suppressed neuronal oscillations. In wild-type mice, perturbation of GRP-BB2 signaling had few effects on SCN cellular rhythms, except when VPAC2 receptors were blocked pharmacologically. These findings establish that residual electrical oscillations persist in the SCN of Vipr2(-/-) mice and reveal a potential new role for GRP-BB2 signaling within the circadian clock.
Brown
Timothy M
TM
Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, United Kingdom.
Hughes
Alun T
AT
Piggins
Hugh D
HD
D000818:Animals; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010507:Periodicity; D018004:Receptors, Bombesin / Q000378:metabolism*; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013493:Suprachiasmatic Nucleus / Q000166:cytology / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D018004:Receptors, Bombesin; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide; D019886:Gastrin-Releasing Peptide