Hippocampal Interneuron Network Dynamics After Epileptogenesis

描述(由申请人提供)： 颞叶癫痫(TLE)是成人中最常见的癫痫形式，也是战争相关脑损伤的常见后果。然而，TLE的潜在机制尚不清楚。人类和动物的研究表明，癫痫脑内海马GABA能中间神经元的解剖连接发生了显著的变化。然而，在清醒行为的癫痫动物中，已发现的海马GABA能中间神经元和锥体神经元的功能连接和同步性尚不清楚。在这里，我们建议使用匹罗卡品的TLE模型，结合细胞旁记录和生物细胞素标记，在球形跑步机上导航的清醒行为小鼠，以检验这一假设，即PV+篮子细胞和锥体神经元的相位锁定放电在theta和Gamma振荡期间病理性地增加，但在涟漪中不改变。我们还将测试这一假设，即SOM+OL-M细胞对theta振荡的锁相精度降低，对伽马振荡没有变化，而在涟漪期间表现出更高的放电率。该方案的实验是专门针对TLE背后的网络机制而设计的。可以预期，明确实验性TLE对海马区GABA能中间神经元和锥体神经元的功能影响将有助于未来开发更好的TLE患者认知功能障碍的治疗方法。)

DESCRIPTION (provided by applicant): Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults and a common outcome of war-related brain trauma. However, the mechanisms underlying TLE are not understood. There is evidence from human and animal studies that there are significant alterations in the anatomical connectivity of hippocampal GABAergic interneurons in epileptic brain. However, the functional connectivity and synchronization of identified hippocampal GABAergic interneurons and pyramidal neurons in awake-behaving epileptic animals are not known. Here we propose to use the pilocarpine model of TLE in combination with juxtacellular recording and biocytin labeling, in awake behaving mice navigating on a spherical treadmill, to test the hypothesis that the phase-locked firing of PV+ basket cell and pyramidal neurons is pathologically increased during theta and gamma oscillations but not altered during ripples. We will also test the hypothesis that SOM+ OL-M cells show decreased precision in phase-locking to theta oscillations, no change to gamma oscillations, and increased firing rates during ripples. The experiments of this proposal are designed to specifically target the network mechanisms underlying TLE. It is anticipated that defining the functional consequences of experimental TLE on GABAergic interneurons and pyramidal neurons in the hippocampus will help the future development of better treatments for cognitive dysfunction suffered by patients with TLE. )