SYNAPTIC CONNECTIVITY IN THE DENTATE GYRUS

齿状回的突触连接

• 批准号: 6540042
• 负责人: HILLARY B MICHELSON
• 金额: $ 20.63万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-30 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540042
• 关键词: GABA receptor; animal tissue; dentate gyrus; electrical measurement; hippocampus; intercellular connection; neural transmission; neurons; neuroregulation; opioid receptor; potassium ion; protein structure; synapses; synaptic vesicles

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.

描述：（逐字摘自申请人摘要）齿状回是 对于门控信息进入海马内三突触至关重要 电路。该提案将检查齿状突触的连接性 脑回，重点关注我们发现的突触新机制 齿状颗粒细胞去极化。我们最近证明了颗粒 细胞通过突触机制去极化，该机制独立于 离子型谷氨酸、GABA A 或 GABA B 受体激活。自从 提交我们的原始提案后，我们发现阿片肽， 与 GABA 一起从肺门中间神经元共同释放，是可能的候选者 产生颗粒细胞突触去极化。在这个修改后的提案中， 我们将描述阿片类药物依赖性颗粒细胞去极化的特征，并且 研究其在正常和病理突触传播中的作用 海马体内的传输。 我们的初步研究将评估各种阿片肽的贡献和 阿片受体。使颗粒细胞去极化。额外的实验 将表征颗粒细胞去极化的离子性质。其他 研究将扩展我们的初步发现，即阿片类药物依赖性颗粒 细胞去极化可以通过电刺激或升高来引起 细胞外K+。几项研究将调查颗粒细胞的作用 突触去极化门控生理和病理生理的进入 突触活动进入海马回路，使用体外和体内 电刺激（点燃）协议。额外的研究将检查 延长癫痫发作活动和突触重组对 颗粒细胞去极化。最后，我们将使用配对录音 单突触耦合细胞直接检查突触连接 齿状颗粒细胞和肺门中间神经元亚型。这些研究共同 应提供描述生成的有价值的信息 阿片类药物依赖性颗粒细胞去极化及其参与正常和 海马的病理生理突触传递。