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

用于操纵离子通道和受体功能的基因编码工具

• 批准号: 8653031
• 负责人: Edward S. Boyden
• 金额: $ 33.17万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653031
• 关键词: AMPA Receptors; Accounting; Adoption; Adverse effects; Affect; Anxiety; Area; Behavior; Behavioral; Biology; Brain; Brain Diseases; Calcium Channel; Cells; Chemicals; Chimeric Proteins; Chloride Ion; Chlorides; Clinical; Complex; Critiques; Custom; Data; Development; Diabetes Mellitus; Disease; Disease model; Drug Addiction; Drug Targeting; Engineering; Epilepsy; Evaluation; Fostering; Funding; Funding Opportunities; Future; GABA Receptor; Halorhodopsins; Hypertension; Individual; Institutes; Ion Channel; Ions; Life; Light; Mediating; Memory; Mental disorders; Methodology; Mission; Molecular; Movement; Mus; Mutagenesis; N-Methyl-D-Aspartate Receptors; Nervous system structure; Neuroglia; Neuromodulator; Neurons; Neurosciences; Neurotransmitter Receptor; Opsin; Optics; Pathology; Pathway interactions; Performance; Pharmaceutical Preparations; Physiologic pulse; Physiological; Physiological Processes; Pilot Projects; Play; Potassium; Potassium Channel; Probability; Prosthesis; Protein Engineering; Proteins; Proton Pump; Pump; Reagent; Research; Risk; Role; Schizophrenia; Science; Sleep Disorders; Sodium; Sodium Channel; Speed; Structure; Study Section; Supplementation; Technology; Testing; Therapeutic; Toxin; United States National Institutes of Health; Update; Vertebral column; Writing; base; cell type; chronic pain; clinically relevant; design; high throughput screening; in vivo; information processing; innovation; meetings; millisecond; nervous system disorder; novel; receptor; receptor function; relating to nervous system; tool; voltage

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.

描述（由申请人提供）：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作用的高速生理过程，它们与许多神经和精神疾病有关，并且它们为治疗这些疾病提供了一组极其重要的药物靶点。为了更好地理解特定离子通道和受体如何影响行为和病理，我们建议设计一个完全基因编码试剂的工具箱，当在大脑中的特定神经元中表达时，能够使用光脉冲以时间精确的方式驱动或阻断特定离子通道和离子型神经递质受体。我们预计这些工具将在基础和临床神经科学以及其他生物学领域得到广泛应用，用于揭示特定离子通道和受体（或其活性水平的变化）在神经计算、行为和疾病状态中所起的作用，并揭示更具体的药物靶点。