Genetically-Encoded Tools for Manipulation of Ion Channel and Receptor Functions

描述（申请人提供）：离子通道和神经递质受体是神经系统中最重要的分子。它们支持使神经元发挥功能的高速生理过程，它们与许多神经和精神疾病有关，它们为治疗这些疾病提供了一套非常重要的药物靶点。为了更好地理解特定离子通道和受体如何促进行为和病理，我们建议设计一个完全遗传编码试剂工具箱，当在大脑中的特定神经元中表达时，使用光脉冲使特定离子通道和嗜离子性神经递质受体以暂时精确的方式被驱动或阻断。我们预计这些工具将广泛应用于基础和临床神经科学，以及生物学的其他领域，以揭示特定离子通道和受体（或其活动水平的变化）在神经计算、行为和疾病状态中的作用，并揭示更具体的药物靶点。

DESCRIPTION (provided by applicant): Ion channels and neurotransmitter receptors are amongst the most important molecules in the nervous system. They support the high-speed physiological processes that enable neurons to function, they are implicated in many neurological and psychiatric disorders, and they present an incredibly important set of drug targets for treating these diseases. In order to enable a better understanding of how specific ion channels and receptors contribute to behaviors and pathologies, we propose to engineer a toolbox of fully genetically encoded reagents that, when expressed in specific neurons in the brain, enable specific ion channels and ionotropic neurotransmitter receptors to be driven or blocked in a temporally precise fashion, using pulses of light. We anticipate that these tools will find widespread use in both basic and clinical neuroscience, and in other fields of biology, for revealing the roles that specific ion channels and receptors (or changes in their activity levels) play in neural computations, behaviors, and disease states, and for revealing more specific drug targets.