INTRACELLULAR SIGNALS FOR LONG TERM SYNAPTIC DEPRESSION

描述：拟议的研究检查细胞内信号传导 小脑浦肯野细胞中的通路参与了 长时程抑郁症（LTD）由连接激活的攀登 纤维（CF）和平行纤维（PF）的兴奋性输入。 的 将被测试的具体假设是， LTD的诱导是由两个细胞内 信号通路，IP 3和钙离子。 更具体地说，LTD 诱导后CFs提高细胞内钙足以允许PF- 产生IP 3，从细胞内释放额外的钙 储存在浦肯野细胞的突触后棘中。 的 建议有四个具体的目标进行调查：1）的作用 代谢型谷氨酸受体（mGluR）在PF信号传导中的作用; 2） 在LTD的诱导过程中，来自IP 3敏感的内部储存的钙; 3)钙对IP_3敏感性钙库钙释放调节 水平;以及4）如果在CF升高细胞内钙水平后发生LTD 足以允许PF产生的IP 3从 细胞内储存。 调查人员试图实现这些目标 目的通过大鼠小脑脑片的一系列实验， 申请人在全细胞记录，离子成像， 共聚焦显微镜和局部闪光光解将应用于 这些实验。

DESCRIPTION: The proposed research examines the intracellular signaling pathways in cerebellum Purkinje cells implicated in the initiation of long-term depression (LTD)by the conjunctive activation of the climbing fibers (CFs) and the parallel fibers (PFs)excitatory inputs. The specific hypothesis that will be tested is that the associative induction of LTD arises from a convergence between two intracellular signaling pathways, IP3 and calcium ions. More specifically, LTD is induced after CFs raise intracellular calcium sufficiently to permit PF- generated IP3 to release additional calcium from the intracellular stores within the postsynaptic spines of the Purkinje cells. The proposal has four specific aims to investigate: 1)the role of metabotropic glutamate receptors (mGluR)in PF signaling; 2)the role of calcium from IP3- sensitive internal stores in the induction of LTD; 3)the regulation of calcium release from IP3 sensitive stores by calcium levels; and 4)if LTD occurs after CFs raise intracellular calcium levels sufficiently to permit PF-generated IP3 to release more calcium from intracellular stores. The investigators seek to achieve these objectives through a series of experiment using rat cerebellar slices. The applicant's expertise with whole-cell recordings, ion imaging, confocal microscopy, and localized flash photolysis will be applied in these experiments.