SYNAPTIC CONNECTIVITY IN THE DENTATE GYRUS

描述：(逐字摘自申请人的摘要)齿状回是 门控信息进入海马三叉神经突触的关键 巡回赛。这项建议将检查齿状回的突触连接。 集中在我们发现突触的一种新机制上 齿状颗粒细胞的去极化。我们最近展示了这种颗粒 细胞通过突触机制去极化，这种机制独立于 离子型谷氨酸、GABA A或GABA B受体激活。自.以来 提交我们最初的提案时，我们发现阿片肽， 与来自肺门中间神经元的GABA共同释放，是可能的候选者 产生颗粒细胞突触去极化。在这份修订后的提案中， 我们将表征阿片依赖颗粒细胞的去极化，以及 探讨其在正常和病理性突触传播中的作用 在海马体内传播。 我们的初步研究将评估各种阿片肽和 阿片受体。至颗粒细胞去极化。额外的实验 将表征颗粒细胞去极化的离子性质。其他 研究将扩大我们的初步发现，阿片依赖颗粒 细胞去极化可以通过电刺激或通过升高 胞外K+。几项研究将探讨颗粒细胞的作用。 突触去极化在门控生理和病理生理入门中的作用 海马区突触活动的体外和体内研究 电刺激(点燃)方案。其他研究将检查 癫痫发作时间延长和突触重组对大鼠脑内神经元的影响 颗粒细胞去极化。最后，我们将使用配对的录音 单突触偶联细胞直接检测突触连接性 齿状颗粒细胞和肺门中间神经元亚型。总而言之，这些研究 应该提供有价值的信息来描述 阿片依赖型颗粒细胞去极化及其参与正常和 海马区的病理生理学突触传递。

DESCRIPTION: (Verbatim from the Applicant's Abstract) The dentate gyrus is critical for gating information entry into the intrahippocampal trisynaptic circuit. This proposal will examine the synaptic connectivity of the dentate gyrus, focusing on our discovery of a novel mechanism of synaptic depolarization of dentate granule cells. We recently demonstrated that granule cells are depolarized by a synaptic mechanism which is independent of ionotropic glutamate, GABA A or GABA B receptor activation. Since the submission of our original proposal, we have found that opioid peptides, co-released along with GABA from hilar interneurons, are the likely candidates generating the granule cell synaptic depolarization. In this revised proposal, we will characterize the opioid-dependent granule cell depolarization, and investigate the its role in the propagation of normal and pathologic synaptic transmission within the hippocampus. Our initial studies will assess the contribution of various opiate peptides and opioid receptors. To the granule cell depolarization. Additional experiments will characterize the ionic nature of the granule cell depolarization. Other studies will extend our preliminary findings that the opioid-dependent granule cell depolarization can be elicited by electrical stimulation or by elevating extracellular K+. Several studies will investigate the role of the granule cell synaptic depolarization in gating the entry of physiologic and pathophysiologic synaptic activity into the hippocampal circuit, using in vitro and in vivo electrical stimulation (kindling) protocols. Additional studies will examine the effects of prolonged seizure activity and synaptic reorganization on the granule cell depolarization. Lastly, we will use paired recordings of monosynaptically coupled cells to directly examine the synaptic connectivity of dentate granule cells and hilar interneuron subtypes. Together, these studies should provide valuable information describing the generation of the opioid-dependent granule cell depolarization, and its involvement in normal and pathophysiologic synaptic transmission in the hippocampus.