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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.

the journal of neuroscience/the journal of neuroscience

Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC<sub>2</sub>Receptor Signaling

Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC2Receptor Signaling

Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC₂Receptor Signaling