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REM的大脑区域是否可以防止癫痫发作。实验将集中在脚桥核（PPT），中脑胆碱能区，密集地支配丘脑。将在健康和癫痫大鼠的丘脑、新皮质和海马中进行电生理和光学记录。主要的动机假设是，REM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神经元损伤，这种损伤部分是由于丘脑中的胆碱能信号引起的。具体目标1.1将测试PPT的电刺激如何影响健康大鼠丘脑中的乙酰胆碱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做出反应的数据库，以便如果发现治疗方案，则可以更好地理解其神经生理学作用机制。第1.2章测试 这些相同的刺激方案是否改变癫痫点燃模型中的癫痫发作阈值。我推测，这些刺激，诱导强烈的丘脑乙酰胆碱结合也将是那些诱导皮质痉挛，最有效地抑制癫痫发作蔓延诱发点燃模型。然后，特定目标2将测试PPT的电刺激是否有效抑制海马内注射红藻氨酸诱导的慢性癫痫模型中的癫痫发作。癫痫发作将被预测 在线，当癫痫发作可能发生时，将给予PPT刺激。这些实验将进一步加深我们对癫痫发作和睡眠之间联系的理解，并将指导未来的临床研究，以评估是否应该在癫痫患者中靶向REM促进大脑区域。

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.