PRESYNAPTIC MECHANISMS IN THE SUPRACHIASMATIC NUCLEUS

描述(申请人摘要)：与…保持适当的时间耦合 环境，神经系统已经进化，可以监控不断变化的条件 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，一种直接的 视网膜神经节细胞向视交叉上核的谷氨酸能投射 核(SCN)。激活其他传入神经通路可以改变 光输入信号。突触前5-HT1B、GABA-B和神经肽Y受体 抑制突触前RHT终末谷氨酸释放并阻断 昼夜节律的光诱导相移。GABA-B的作用机制， 5-HT1B和神经肽Y受体对谷氨酸释放的抑制作用 为人所知。孤啡肽-FQ受体抑制谷氨酸的释放 突触前RHT终末也将被研究。这些多重传入是如何 输入相互作用调节RHT活性的研究还没有在体内或 在试管中。因此，我们设计了使用电生理的实验 描述突触前通路使用的细胞机制的技术 调节RHT活性和环境光信号。一片一片的 含有SCN和视神经的下丘脑将被用来 通过记录诱发电位和诱发电位来研究谷氨酸的释放特性 自发兴奋性突触后电流。该提案的具体目的 1)确定调节钙离子释放的钙通道亚型 突触前RHT终末的谷氨酸。2)确定机构耦合 GABA-B、5-羟色胺和神经肽Y受体的激活及其抑制作用 突触前RHT终末释放谷氨酸。3)检查孤儿是否 FQ受体对RHT终末产生突触前抑制。4)调查 突触前神经元之间是否存在协同作用 调节RHT终末谷氨酸释放的神经递质受体。

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.