A rat model of responsive neural treatment for epilepsy

该项目的目的是研究为什么快速眼动（REM）睡眠是一种抗惊厥状态，并测试刺激促进快速眼动的大脑区域是否能预防癫痫发作。实验将集中在桥脚核（PPT）上，这是一个中脑胆碱能区域，密集地支配着丘脑。将对健康和癫痫大鼠的丘脑、新皮层和海马体进行电生理和光学记录。核心的激励假说是，快速眼动是一种神经保护状态，这是由于在这种状态下观察到的广泛的皮层不同步，部分原因是丘脑中的胆碱能信号。特异性Aim 1.1将测试电刺激PPT如何影响健康大鼠丘脑中乙酰胆碱的结合以及皮质和丘脑神经元的放电模式。这些实验将建立一个关于大脑如何对不同类型的刺激作出反应的数据库，这样，如果发现一种治疗方案，就可以更好地理解其作用的神经生理机制。具体的Aim 1.2将测试

The aim of this project is to study why rapid eye movement (REM) sleep is an anticonvulsant state and to test whether stimulation of REM-promoting brain regions prevents seizures. Experiments will focus on the pedunculopontine nucleus (PPT), a midbrain cholinergic region that densely innervates the thalamus. Electrophysiological and optical recordings will be done in the thalamus, neocortex, and hippocampus in healthy and epileptic rats. The central motivating hypothesis is that REM is a neuroprotective state due to the wide-spread cortical asynchrony observed in this state which arises, in part, due to cholinergic signaling in the thalamus. Specific Aim 1.1 will test how electrical stimulation of the PPT affects acetylcholine binding in the thalamus and the firing patterns of cortical and thalamic neurons in healthy rats. These experiments will establish a database of how the brain reacts to different kinds of stimulations so that if a therapeutic protocol is discovered, its neurophysiological mechanism of action can be better understood. Specific Aim 1.2 will test whether these same stimulation protocols change the seizure threshold in the kindling model of epilepsy. I hypothesize that those stimulations that induce strong thalamic acetylcholine binding will also be those that induce cortical asynchrony and most effectively suppress seizure spread in the evoked kindling model. Specific Aim 2 will then test whether electrical stimulation of the PPT is effective in suppressing seizures in a chronic epilepsy model induced by intra-hippocampal kainic acid injection. Seizures will be predicted online, and stimulation of the PPT will be given when seizures are likely. These experiments will further our understanding of the link between seizures and sleep and will guide future clinical studies to assess whether REM promoting brain regions should be targeted in patients suffering from epilepsy.