Targeted interneuron ablation and epileptogenesis

描述（由申请方提供）：GABA能中间神经元的缺失是颞叶癫痫的主要特征，在人类患者和动物模型中均如此。这项研究的目的是确定选择性的局灶性中间神经元损伤是否会导致发作间期 痉挛和癫痫这项研究将测试的假设，中间神经元的损失，独立于其他局部电路机制，有助于显着的癫痫发作的产生。拟议的研究将利用神经毒素方法以及独立的遗传技术来选择性地消融中间神经元。这两种方法最初将损害异质群体的中间神经元，但随后的研究将集中在特定的子类型的中间神经元。在中间神经元消融后，将进行连续的体内视频LFP监测，并对剩余主细胞及其网络的电生理特性进行体外评估。这些实验的结果将提高我们对GABA能中间神经元的丢失在癫痫发作和癫痫发生中的作用的理解。

DESCRIPTION (provided by applicant): Loss of GABAergic interneurons is a major feature of temporal lobe epilepsy, both in human patients as well as animal models. The aim of the proposed research is to determine whether selective, focal interneuron lesions result in interictal spikes and seizures. This research will test the hypothesis that interneuron loss, independent of other local-circuit mechanisms, contributes significantly to the generation of epileptic seizures. The proposed studies will utilize a neurotoxin approach, as well as an independent genetic technique, to selectively ablate interneurons. The two approaches will initially lesion heterogeneous populations of interneurons, but subsequent studies will focus on specific sub-types of interneurons. The interneuron ablations will be followed by continuous in vivo video-LFP monitoring and in vitro assessment of the electrophysiological properties of the remaining principal cells and their networks. The results of these experiments will improve our understanding of the role that the loss of GABAergic interneurons plays in seizure generation and epileptogenesis.