Abstract
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-BB 2 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. Copyright © 2005 Society for Neuroscience.
| Original language | English |
|---|---|
| Pages (from-to) | 11155-11164 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience |
| Volume | 25 |
| Issue number | 48 |
| DOIs | |
| Publication status | Published - 30 Nov 2005 |
Keywords
- BB2 receptor
- Circadian
- Electrophysiology
- Entrainment
- Hypothalamus
- VIP
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Centre for Biological Timing
Lucas, R. (PI), Bechtold, D. (PI), Fustin, J.-M. (PI), Ashe, H. (PI), Brown, T. (PI), Blaikley, J. (PI), Brass, A. (PI), Chandola, T. (PI), Durrington, H. (PI), Else, K. (PI), Hepworth, M. (PI), Hunter, L. (PI), Kadler, K. (PI), Kitchen, G. (PI), Loudon, A. (PI), Macdonald, A. (PI), Mcbeth, J. (PI), Milosavljevic, N. (PI), Rattray, M. (PI), Rutter, M. (PI), Sharrocks, A. (PI), Spiller, D. (PI), Storchi, R. (PI), Belle, M. (PI), Meng, Q.-J. (PI), Allen, A. (PI), Dixon, W. (PI), Gibbs, J. (PI), Hazel, A. (PI), Papalopulu, N. (PI), Ray, D. (PI), White, M. (PI) & Chang, J. (PI)
Project: Research