A rat model of responsive neural treatment for epilepsy

癫痫反应性神经治疗大鼠模型

• 批准号: 10384002
• 负责人: Samuel Arnold McKenzie
• 金额: $ 12.79万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-02-10 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10384002
• 关键词: rat; model; responsive; neural; treatment

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.

这个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。实验将集中在桥脑脚核(PPT)，这是一个密集支配丘脑的中脑胆碱能区域。将在健康和癫痫大鼠的丘脑、新皮质和海马区进行电生理和光学记录。主要的激励假设是，REM是一种神经保护状态，因为在这种状态下观察到广泛的皮质不同步，部分原因是丘脑中的胆碱能信号。具体目标1.1将测试电刺激PPT如何影响健康大鼠丘脑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大脑如何对不同类型的刺激做出反应的数据库，这样如果发现了一种治疗方案，就可以更好地了解其神经生理作用机制。特定目标1.2将测试 这些相同的刺激方案是否改变了癫痫点燃模型中的癫痫发作阈值。我推测，在诱发性点燃模型中，那些诱导丘脑乙酰胆碱强烈结合的刺激也将是那些诱导皮质异步化和最有效地抑制癫痫发作扩散的刺激。然后，《特定目标2》将测试电刺激PPT是否能有效抑制海人酸海人酸海人酸慢性癫痫模型的发作。癫痫发作是可以预测的 在网上，当有可能癫痫发作时，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，以评估是否应该将促进快速眼动的大脑区域作为癫痫患者的目标。