Characterization of CA 1 hippocampal interneuron LTD

描述（由候选人提供）：海马中间神经元由于反应下降导致的神经病理学可导致失控活动导致癫痫，而活动增加消除了海马theta节律，这在阿尔茨海默病患者中是不存在的。因此，了解中间神经元活动水平如何维持锥体细胞的适当反馈控制是非常重要的。长期增强和抑制（LTP/LTD）是一种活动依赖性的突触变化，改变神经元的活动，并由AMPA谷氨酸受体进入或离开突触介导。令人惊讶的是，尽管它们的重要性显而易见，但人们对海马中间神经元的LTD诱导机制知之甚少。该应用程序将使用全细胞电生理学、分子生物学（RT-PCR）和药理学来测试以下目标：(1)确定显示LTD的中间神经元亚类，以及它是否发生在缺乏GluR2 AMPA受体亚基的细胞中；(2)确定触发该LTD所需的信号级联；(3)确定突触后或突触前结构域是LTD修饰的位点。综上所述，了解中间神经元有限的调节机制对于纠正海马中间神经元功能障碍非常重要。

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.