Roles of GABA and VIP in the Suprachiasmatic Nucleus

描述(申请人提供)：在哺乳动物中，位于下丘脑视交叉上核(SCN)的昼夜节律起搏器调节日常行为和生理节律。单个SCN神经元以近24小时的周期有节奏地放电。目前尚不清楚这些神经元如何在SCN网络内进行通信以产生同步的昼夜节律。参与组织水平节律的血管活性肠多肽(VIP)和GABA可能是单个SCN神经元节律性或同步性所必需的。确定这些递质如何影响单个SCN神经元的节律，对于了解SCN网络如何产生协调的节律输出至关重要。我们将使用多电极阵列技术记录单个SCN神经元的放电频率节律，并结合旨在阻断或模仿GABA和VIP信号的遗传和药物操作。这些实验将直接确定哪些SCN神经元具有细胞自主起搏能力，并测试是否需要GABA或VIP信号来维持它们之间的同步性或驱动它们的节律性。我们的发现将有助于开发治疗昼夜节律紊乱的新药物干预措施。

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.