An optogenetic brain implant with EEG monitoring and response for mice

具有脑电图监测和小鼠反应功能的光遗传学脑植入物

• 批准号: 9909902
• 负责人: Kevan Sayed Hashemi
• 金额: $ 30.26万
• 依托单位: OPEN SOURCE INSTRUMENTS, INC.
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-16 至 2020-12-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9909902
• 关键词: Address; Algorithms; Alzheimer' s Disease; Archives; Area; Arrhythmia; Basic Science; Biological Assay; Biology; Brain; Brain Diseases; Brain region; Cells; Characteristics; Chlorides; Chronic; Classification; Computer software; Coupled; Data; Detection; Development; Devices; Disease; Disease model; Electroencephalography; Electrophysiology (science); Epilepsy; Equipment; Event; Exhibits; Feedback; Fiber; Focal Seizure; Goals; Halorhodopsins; Hour; Human; Implant; Implantable Defibrillators; Individual; Interneurons; Interruption; Intervention; Iron; Left; Light; Lighting; Logic; Medical; Medical Device; Mental Depression; Monitor; Mouse Strains; Mus; Neurologic; Neurons; Obsessive-Compulsive Disorder; Optics; Parkinson Disease; Partial Epilepsies; Patients; Pattern; Pharmacologic Substance; Pharmacological Treatment; Phase; Photosensitivity; Physiologic pulse; Play; Proteins; Rattus; Reporting; Research; Research Personnel; Resistance; Sales; Scheme; Schizophrenia; Seizures; Site; Specificity; System; Technology; Testing; Time; Transgenic Animals; Transgenic Mice; Transgenic Organisms; Viral; Wireless Technology; base; data acquisition; design; experimental study; hippocampal pyramidal neuron; human disease; human model; in vivo; inhibitory neuron; instrument; mouse model; neocortical; neural circuit; neural implant; neuropsychiatric disorder; optogenetics; promoter; response; subcutaneous; theories

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).

翻译后摘要：光遗传学可以用来选择性地刺激或抑制基因的发射 靶向和空间靶向哺乳动物神经元。它是用来研究神经精神的 用包括癫痫、精神分裂症和精神分裂症在内的病症的小鼠模型进行体内疾病研究， 帕金森等光遗传学可用作功能性神经外科干预， 大脑中的疾病状态。以前已经表明，癫痫发作有能力被 通过使用抑制性神经元的光遗传学激活而停止或减少 视紫红质-2也已经表明，在皮质中表达盐视紫红质（HR）， 锥体神经元也可以减少癫痫发作的传播。通过真实的实时监测EEG数据， 癫痫发作可以在其发作时被识别， 应用。这一研究领域目前因缺乏适当的工具而受到限制。这个项目 建议开发一种完全植入式无线EEG监测仪， 实时自主检测EEG事件，并应用 闭环光遗传学刺激。拟议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 可用于光敏蛋白质，并被验证为人类疾病的模型。目标1将 通过结合现有的核心技术，开发必要的硬件， 产品. Aim 2将在仪器的微功率下实现自主EEG事件检测 逻辑芯片通过采用计算效率高的算法，已被证明能够 分类EEG事件，包括正常活动、癫痫发作、发作尖峰、发作间尖峰，以及 多刺突。目标3将测试该设备检测癫痫发作的能力， 刺激，并减少小鼠中通过纳米注射 氯化铁该项目的第一阶段将使鼠标兼容的仪器可用于 销售给研究大脑回路理论和疾病/紊乱的研究人员， 异常脑电图状态，如癫痫、精神分裂症、阿尔茨海默氏症和强迫症 disorder.潜在的后续第二阶段将把这项技术发展成一种医疗仪器 使患有耐药性部分性癫痫的人的局灶性癫痫发作中止 （约1500万人）。