An optogenetic brain implant with EEG monitoring and response for mice

摘要：光遗传学可用于选择性地刺激或抑制基因的fi环。 靶向和空间靶向的哺乳动物神经元。它被用来研究神经精神病学 体内疾病的小鼠模型包括癫痫，精神分裂症，和 光遗传学可用于功能性神经外科手术矫正帕金森氏症 大脑中的疾病状态。此前已有研究表明，癫痫发作有能力 通过利用光发生激活抑制神经元而停止或减少 通道视紫红质-2。也有研究表明，在大脑皮层表达卤视紫质(HR) 锥体神经元也可以减少癫痫的传播。通过实时监控脑电数据， 癫痫发作可以在发作时被识别，纠正光遗传刺激的脉冲可能是 已申请。目前，由于缺乏合适的工具，这一研究领域受到限制。这个项目 建议开发一种完全可植入的无线脑电监护仪，能够 自动实时检测脑电事件并施加校正脉冲 闭合环光遗传刺激。所提出的仪器将与鼠标兼容 生物学，从而允许在巨大的转基因小鼠品系库中进行长期实验 可用于光敏蛋白，并被验证为人类疾病的模型。目标1将 通过结合现有的 产品。AIM 2将在仪器的微功率中实现自主脑电事件检测 通过采用一种计算效率高的算法来实现逻辑芯片 对脑电事件进行分类，包括正常活动、癫痫发作、发作性尖峰、发作间歇性尖峰和 多个尖峰。AIM 3将测试该设备检测癫痫发作的能力，应用矫正光遗传 刺激，并缩短小鼠局灶性癫痫发作的持续时间 氯化铁。该项目的第一阶段将使鼠标兼容仪器可用于 卖给研究大脑回路理论和疾病/障碍的研究人员 异常脑电状态，如癫痫、精神分裂症、阿尔茨海默氏症和强迫症 无序。潜在的第二阶段将把这项技术开发成一种医疗器械 该药可使耐药部分性癫痫患者的局灶性癫痫发作流产 (大约1500万人)。

Abstract: Optogenetics can be used to selectively stimulate or suppress the firing of genetically targeted and spatially targeted mammalian neurons. It is used to study neuropsychiatric diseases in vivo with mouse models of conditions including epilepsy, schizophrenia, and Parkinson's. Optogenetics may be used as functional neurosurgical intervention for correcting disease states in the brain. It has been previously shown that seizures have the ability to be halted or reduced by optogenetic activation of inhibitory neurons with the use of Channelrhodopsin-2. It has also been shown that expressing Halorhodopsin (HR) in cortical pyramidal neurons can also reduce seizure propagation. By monitoring EEG data in real time, seizures can be identified at their onset and correcting pulses of optogenetic stimulation may be applied. This line of research is currently limited by the lack of suitable instruments. This project proposes the development of a fully implantable, wireless EEG monitor capable of autonomously detecting EEG events in real-time and applying correcting pulses of closed-loop optogenetic stimulation. The proposed instrument will be compatible with mouse biology, thus permitting chronic experiments in the enormous pool of transgenic mouse strains available with photosensitive proteins and validated as models of human disease. Aim 1 will develop the necessary hardware by combining core technologies demonstrated in existing products. Aim 2 will enable autonomous EEG event detection in the instrument's micropower logic chip by adapting a computationally efficient algorithm that has been proven capable of classifying EEG events including normal activity, seizures, ictal spikes, inter-ictal spikes, and polyspikes. Aim 3 will test the device's ability to detect seizures, apply correcting optogenetic stimulation, and reduce the duration of focal seizures induced in mice by the nanoinjection of iron chloride. Phase I of this project will make the mouse-compatible instrument available for sale to researchers studying circuit theory of the brain and diseases/disorders characterized by aberrant EEG states such as epilepsy, schizophrenia, Alzheimer's, and obsessive compulsive disorder. Potential follow-on Phase II would develop the technology into a medical instrument that aborts focal seizures in humans who suffer from pharmaceutical-resistant partial epilepsy (approximately 15 million people).