Characterization of CA 1 hippocampal interneuron LTD

描述（由候选人提供）：海马中间神经元的神经病理学，由于反应降低，可导致失控活动引起癫痫，而增加的活动消除海马θ节律，这是阿尔茨海默氏症患者中不存在的。 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。 长时程增强和抑制（LTP/LTD）是改变神经元活动的活动依赖性突触变化，并且由AMPA谷氨酸受体运动进入或离开突触介导。 令人惊讶的是，尽管其明显的重要性是鲜为人知的LTD诱导机制在海马中间神经元。 本申请将使用全细胞电生理学、分子生物学（RT-PCR）和药理学测试以下目的：（1）确定展示LTD的中间神经元亚类以及其是否发生在缺乏GluR 2 AMPA受体亚单位的细胞中，（2）确定触发该LTD所需的信号级联，以及（3）确定突触后或突触前结构域是否是LTD修饰的位点。 总的来说，了解介导中间神经元LTD的机制对于纠正海马中的中间神经元功能障碍将是重要的。

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.