Disrupted Neuronal Activity Rhythms in the Suprachiasmatic Nuclei of Vasoactive Intestinal Polypeptide-Deficient Mice

• Published in: Journal of neurophysiology Vol. 97; no. 3; pp. 2553 - 2558
• Main Authors: Brown, T. M, Colwell, C. S, Waschek, J. A, Piggins, H. D
• Format: Journal Article
• Language: English
• Published: United States Am Phys Soc 01.03.2007
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Analysis of Variance; Animals; Chi-Square Distribution; Circadian Rhythm - drug effects; Circadian Rhythm - genetics; Female; In Vitro Techniques; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Neurons - drug effects; Neurons - physiology; Receptors, Vasoactive Intestinal Peptide, Type II - antagonists & inhibitors; Suprachiasmatic Nucleus - cytology; Vasoactive Intestinal Peptide - deficiency
• ISSN: 0022-3077; 1522-1598
• DOI: 10.1152/jn.01206.2006

1 Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom; and 2 Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California Submitted 15 November 2006; accepted in final form 5 December 2006 Vasoactive intestinal polypeptide (VIP), acting via the VPAC 2 receptor, is a key signaling pathway in the suprachiasmatic nuclei (SCN), the master clock controlling daily rhythms in mammals. Most mice lacking functional VPAC 2 receptors are unable to sustain behavioral rhythms and lack detectable SCN electrical rhythms in vitro. Adult mice that do not produce VIP (VIP/PHI –/– ) exhibit less severe alterations in wheel-running rhythms, but the effects of this deficiency on the amplitude, phasing, or periodicity of their SCN cellular rhythms are unknown. To investigate this, we used suction electrodes to extracellularly record multiple- and single-unit electrical activity in SCN brain slices from mice with varying degrees of VIP deficiency, ranging from wild-type (VIP/PHI +/+ ) to heterozygous (VIP/PHI +/– ) and VIP/PHI –/– animals. We found decreasing proportions of rhythmic cells in SCN slices from VIP/PHI +/+ ( 91%, n = 23) through VIP/PHI -/+ ( 71%, n = 28) to VIP/PHI –/– mice (62%; n = 37) and a parallel trend toward decreasing amplitude in the remaining rhythmic cells. SCN neurons from VIP/PHI –/– mice exhibited a broad range in the period and phasing of electrical rhythms, concordant with the known alterations in their behavioral rhythms. Further, treatment of VIP/PHI –/– slices with a VPAC 2 receptor antagonist significantly reduced the proportion of oscillating neurons, suggesting that VPAC 2 receptors still become activated in the SCN of these mice. The results establish that VIP is important for appropriate periodicity and phasing of SCN neuronal rhythms and suggest that residual VPAC 2 receptor signaling promotes rhythmicity in adult VIP/PHI –/– mice. Address for reprint requests and other correspondence: H. D. Piggins, Faculty of Life Sciences, University of Manchester, Manchester, UK M139PT (E-mail: hugh.piggins{at}manchester.ac.uk )