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Optogenetic hub cell control for no seizures, no side-effects temporal lobe epilepsy

光遗传学中心细胞控制无癫痫发作，无副作用颞叶癫痫

基本信息

批准号：
9165938
负责人：
IVAN SOLTESZ
金额：
$ 0.49万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-21 至 2016-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9165938
关键词：
Optogenetic hub cell control no

项目摘要

Temporal lobe epilepsy is the most common form of epilepsy in adults. Currently available anti-epileptic drugs often have significant and debilitating side-effects, and temporal lobe epilepsy frequently becomes resistant to drug therapy, presenting an enormous social and medical problem. The central idea behind the proposed research is that it may be possible to achieve seizure control by transiently inhibiting, only at critical moments, the activity of a low number of unique neurons that may be primarily responsible to triggering seizures in the limbic system. Our recent large-scale computational modeling studies have shown that rare, abnormal, super- connected, hub-like neurons may play a key role in seizure initiation. Subsequently, such hub cells have been demonstrated in the healthy developing hippocampus, and it has been shown that modulation of single hub cells in slices can block the spontaneous bursting activity of the entire network. Here we propose to use novel optogenetic approaches to selectively inhibit abnormal hub-like cells in the dentate gyrus and entorhinal cortex of epileptic adult mice in vivo in order to prevent the hyper-activation of the commissural-associational and temporo-ammonic pathways within the entorhino-hippocampal network specifically at the onset of spontaneous recurrent seizures. Because the manipulation will affect only a few cells in the entire limbic system in a temporally selective manner, effective seizure control may be achieved with minimal effects on the normal information processing of the circuit. If successful, the proposed research will demonstrate a fundamentally novel approach to achieving the goal of “no seizures, no side-effects” for the treatment of epilepsy.

颞叶癫痫是成人癫痫最常见的形式。目前可用的抗癫痫药物往往有显着的和衰弱的副作用，颞叶癫痫往往成为抵抗，药物治疗，呈现出巨大的社会和医学问题。建议背后的中心思想是研究表明，只有在关键时刻，少数独特神经元的活动可能主要负责触发癫痫发作，边缘系统我们最近的大规模计算建模研究表明，罕见的，异常的，超连接的中枢样神经元可能在癫痫发作起始中起关键作用。随后，这样的中枢细胞已经被在健康发育的海马体中证实了这一点，并且已经表明，切片中的细胞可以阻断整个网络的自发爆发活动。在这里，我们建议使用新的选择性抑制齿状回和内嗅皮层异常中枢样细胞的光遗传学方法癫痫成年小鼠体内，以防止过度激活的连合联合和内鼻-海马网络内的颞-氨途径，特别是在自发性反复发作因为这种操作只会影响整个边缘系统中的几个细胞，时间选择性的方式，可以实现有效的癫痫控制，对正常的影响最小电路的信息处理。如果成功，拟议的研究将从根本上证明为达到“无发作、无副作用”的癫痫治疗目标提供了一种新的方法。