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，也是战争相关脑外伤的常见结果。然而，TLE的潜在机制尚不清楚。人类和动物研究的证据表明，癫痫脑中海马GABA能中间神经元的解剖连接存在显著改变。然而，在清醒行为的癫痫动物中，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TLE的毛果芸香碱模型与aptacellular记录和biocytin标记相结合，在清醒的行为小鼠在球形跑步机上导航，以测试的假设，即PV+篮状细胞和锥体神经元的锁相发射在θ和γ振荡过程中病理性增加，但在涟漪过程中不改变。我们还将测试的假设，SOM+ OL-M细胞显示降低的相位锁定θ振荡的精度，没有变化的伽马振荡，并增加发射率在纹波。这个建议的实验是专门针对TLE的网络机制。可以预期，确定实验性TLE对海马中GABA能中间神经元和锥体神经元的功能后果将有助于未来开发更好的治疗TLE患者认知功能障碍的方法。 )

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. )