SYNAPTIC CONNECTIVITY IN THE DENTATE GYRUS

描述：（申请人摘要中的逐字记录）齿状回是 对于海马内三突触的门控信息输入至关重要 电路.这项提议将研究齿状回的突触连接 脑回，重点是我们发现的一种新的机制， 齿状颗粒细胞的去极化。我们最近证明了这种颗粒 细胞通过突触机制去极化， 离子型谷氨酸、GABA A或GABA B受体活化。以来 在提交我们最初的提案时，我们发现阿片肽， 与来自门部中间神经元的GABA共同沿着释放的是可能的候选者 产生颗粒细胞突触去极化。在这一修订提案中， 我们将描述阿片依赖性颗粒细胞去极化的特征， 研究其在正常和病理性突触传播中的作用， 海马体内的信号传输 我们的初步研究将评估各种阿片肽的贡献， 阿片受体颗粒细胞去极化。另外的实验 将表征颗粒细胞去极化的离子性质。其他 研究将扩展我们的初步发现， 细胞去极化可以通过电刺激或通过升高 胞外K+。一些研究将探讨颗粒细胞的作用 突触去极化门控进入生理和病理生理 突触活动进入海马电路，在体外和体内使用 电刺激（点燃）方案。更多的研究将检查 长时间的癫痫发作活动和突触重组对 颗粒细胞去极化最后，我们将使用成对的录音， 单突触偶联细胞直接检查突触连接 齿状颗粒细胞和门部中间神经元亚型。这些研究一起 应该提供有价值的信息，描述 阿片样物质依赖性颗粒细胞去极化，及其参与正常和 海马中的病理生理突触传递。

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.