PRESYNAPTIC MECHANISMS IN THE SUPRACHIASMATIC NUCLEUS

描述（申请人摘要）：为了保持与 环境，神经系统已经进化，监测不断变化的条件 并将信息传递给生物钟。这个生物钟 通过视网膜下丘脑束（RHT）感觉昼夜转换， 视网膜神经节细胞向视交叉上核的神经投射 核（SCN）。其他传入神经通路的激活可以改变 光输入信号。突触前5-HT 1B、GABA-B和神经肽Y受体 抑制突触前RHT末梢谷氨酸释放，阻断 光诱导的昼夜节律相移。GABA-B的作用机制， 5-HT 1B和神经肽Y受体对谷氨酸释放的抑制作用不 知道的谷氨酸受体对谷氨酸释放的抑制作用 还将研究突触前RHT末梢。这些多个传入神经 输入相互作用调节RHT活性还没有在体内研究， 体外因此，我们设计了实验， 技术来描述突触前通路的细胞机制， 调节RHT活性和环境光信号。的切片 下丘脑含有SCN与视神经连接将用于 用记录诱发电位和 自发兴奋性突触后电流。提案的具体目标 1）识别调节钙离子释放的钙通道亚型， 来自突触前RHT末梢的谷氨酸盐。2)确定机构耦合 GABA-B、5-HT和神经肽Y受体的激活， 突触前RHT末梢释放谷氨酸。3)检查是否存在 FQ受体对RHT末梢产生突触前抑制。4)探讨 突触前神经元之间是否存在协同作用 神经递质受体调节谷氨酸从RHT终端的释放。

DESCRIPTION (applicant's abstract): To maintain proper temporal coupling with the environment, neural systems have evolved that monitor changing conditions and communicate the information to the circadian clock. This biological clock senses day-night transitions via the retinohypothalamic tract (RHT), a direct glutamatergic projection from retinal ganglion cells to the suprachiasmatic nucleus (SCN). Activation of other afferent neural pathways can modify the light input signal. Presynaptic 5-HT1B, GABA-B, and neuropeptide Y receptors inhibit glutamate release from presynaptic RHT terminals and block light-induced phase shifts of circadian rhythms. The mechanisms of GABA-B, 5-HT1B, and neuropeptide Y receptor inhibition of glutamate release are not known. The inhibition of glutamate release by orphanin-FQ receptors at presynaptic RHT terminals will also be studied. How these multiple afferent inputs interact to regulate RHT activity has not been studied either in vivo or in vitro. Therefore, we have designed experiments using electrophysiological techniques to describe the cellular mechanisms presynaptic pathways use to modulate RHT activity and the environmental light signal. Slices of the hypothalamus containing the SCN with the optic nerve attached will be used to investigate the characteristics of glutamate release by recording evoked and spontaneous excitatory postsynaptic currents. The specific aims of the proposal are: 1) Identify the calcium channel subtypes that regulate the release of glutamate from presynaptic RHT terminals. 2) Determine the mechanisms coupling activation of GABA-B, 5-HT, and neuropeptide Y receptors with the inhibition of glutamate release from presynaptic RHT terminals. 3) Examine whether orphanin FQ receptors produce presynaptic inhibition of RHT terminals. 4) Investigate whether there are co-operative interactions between presynaptic neurotransmitter receptors regulating glutamate release from RHT terminals.