Roles of GABA and VIP in the Suprachiasmatic Nucleus

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DESCRIPTION (provided by applicant): In mammals, a circadian pacemaker in the suprachiasmatic nucleus (SCN) of the hypothalamus mediates daily rhythms in behavior and physiology. Individual SCN neurons fire rhythmically with near-24-hour periodicity. It is not known how these neurons communicate within the SCN network to produce synchronous circadian rhythmicity. Vasoactive intestinal polypeptide (VIP) and GABA, implicated in tissue level rhythms, may be required for rhythmicity in, or synchrony among, individual SCN neurons. Determining how these transmitters affect the rhythms of individual SCN neurons is critical to understanding how coordinated rhythmic output is generated by the SCN network. We will employ multi-electrode array technology to record firing rate rhythms of single SCN neurons, in conjunction with genetic and pharmacologic manipulations aimed at blocking or mimicking GABA and VIP signaling. These experiments will directly identify which SCN neurons have cell-autonomous pacemaking ability, and test whether GABA or VIP signaling is needed to maintain synchrony between them or drive their rhythmicity. Our findings will facilitate the development of novel drug interventions for the treatment of circadian rhythm disorders.