Characterization of CA 1 hippocampal interneuron LTD

CA 1 海马中间神经元 LTD 的表征

• 批准号: 6886337
• 负责人: JEFFREY G EDWARDS
• 金额: $ 3.08万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-01-01 至 2005-08-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6886337
• 关键词: AMPA receptors; electrophysiology; hippocampus; interneurons; laboratory rat; long term potentiation; membrane potentials; neural plasticity; neural transmission; neuropharmacology; polymerase chain reaction; postdoctoral investigator

DESCRIPTION (provided by candidate): Neuropathology of hippocampal interneurons due to decreased response can result in run-away activity causing epilepsy, while increased activity eliminates the hippocampal theta rhythm, which is absent in Alzheimer's patients. Therefore, understanding how interneurons activity levels maintain the appropriate feedback control of pyramidal cells is extremely important. Long-term potentiation and depression (LTP/LTD) are activity-dependent synaptic changes that alter neuronal activity, and are mediated by AMPA glutamate receptor movement into or out of a synapse. Surprisingly, despite their obvious importance little is known about the LTD induction mechanism within hippocampal interneurons. This application will test the following aims using whole cell electrophysiology, molecular biology (RT-PCR) and pharmacology: (1) determine the interneuron subclass displaying LTD and whether it occurs in cells lacking GluR2 AMPA receptor subunits, (2) determine the signaling cascade required to trigger this LTD, and (3), establish whether the postsynaptic or presynaptic domain is the site of LTD modification. Collectively, understanding the mechanisms mediating interneuron LTD will be important to correct for interneuron dysfunction in the hippocampus.

描述(由Candiate提供)：由于反应降低而导致的海马区中间神经元的神经病理可以导致失控的活动导致癫痫，而活动增加则消除了海马theta节律，这在阿尔茨海默氏症患者中是不存在的。因此，了解中间神经元的活动水平如何维持锥体细胞的适当反馈控制是极其重要的。长时程增强和长时程增强抑制(LTP/LTD)是一种活性依赖的突触改变，通过AMPA谷氨酸受体移入或移出突触来改变神经元的活性。令人惊讶的是，尽管它们具有明显的重要性，但对海马区中间神经元中LTD的诱导机制知之甚少。这项应用将利用全细胞电生理学、分子生物学(RT-PCR)和药理学来测试以下目标：(1)确定神经元间亚类显示LTD以及它是否发生在缺乏GluR2 AMPA受体亚基的细胞中，(2)确定触发LTD所需的信号级联，以及(3)确定突触后或突触前区域是LTD修饰的位置。总而言之，了解介导中间神经元LTD的机制对于纠正海马区中间神经元功能障碍将是重要的。