Core 1: Brain Circuit Validation Core

核心1：脑回路验证核心

• 批准号: 10090540
• 负责人: Thomas L. Kash
• 金额: $ 22.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10090540
• 关键词: Affect; Agonist; Alcohol abuse; Alcohol consumption; Alcohols; Anatomy; Animal Model; Awareness; Brain; Brain region; Cell physiology; Chronic; Custom; Data; Designer Drugs; Drug usage; Electrophysiology (science); Ensure; Enterobacteria phage P1 Cre recombinase; Fluorescence Microscopy; Fluorescent in Situ Hybridization; G-Protein-Coupled Receptors; Goals; Immunohistochemistry; Injections; Label; Literature; Maintenance; Measures; Mus; Neurons; Other Genetics; Periodicity; Physiological; Physiology; Population; Process; Quality Control; Reagent; Relapse; Reproducibility of Results; Research Personnel; Scanning; Serotyping; Services; Site; Slice; Stress; Synaptic Transmission; Techniques; Testing; Validation; Viral; Virus; Work; alcohol behavior; alcohol exposure; alcohol seeking behavior; base; cell type; depressive symptoms; drug action; experimental group; genetic approach; in vivo; interest; mouse Cre recombinase; neuronal circuitry; neuronal excitability; neuroregulation; nonhuman primate; postsynaptic; presynaptic; protein expression; receptor; tool; vector

Chronic ethanol exposure and stress alter synaptic transmission and neuronal excitability in a number of brain circuits that control acquisition, maintenance, relapse and escalation of ethanol seeking and drinking. Work from previous INIA cycles/projects has generated hypotheses about how specific physiological changes in defined neuronal populations and circuits affect these ethanol-related behaviors. In the INIA-Stress renewal, multiple projects will test these hypotheses by manipulating and measuring neuronal and circuit function using multiple viral based genetic approaches in several distinct mouse Cre- recombinase driver lines. The central goal of this core is to provide initial validation of all mouse lines, and ongoing validation of all viral tools used in the consortium. While multiple viral tools will be validated, the Designer Receptor Activated by Designer Drug (DREADD) based chemogenetic approach has emerged as a common tool across multiple projects and will represent the bulk of the effort. The DREADD technique, based on neuromodulation by G protein-coupled receptors, has many attractive features for neuron/circuit control and has been shown to be highly effective for probing circuit function in animal models. The services of this core will be provided to fill significant gaps in the literature and provide assistance to many of the INIA-Stress projects.

慢性乙醇暴露和应激改变突触传递和神经元兴奋性在一些 大脑回路控制乙醇寻求的获取、维持、复发和升级， 喝酒之前INIA周期/项目的工作已经产生了关于具体程度的假设 确定的神经元群体和回路中的生理变化影响这些乙醇相关行为。 在INIA-Stress更新中，多个项目将通过操作和测量来测试这些假设。 在几种不同的小鼠Cre中使用多种基于病毒的遗传方法实现神经元和电路功能 重组酶驱动线。该核心的中心目标是提供所有小鼠品系的初始验证， 并对联盟中使用的所有病毒工具进行持续验证。虽然多种病毒工具将 经验证，基于化学遗传学方法的设计者药物激活的设计者受体（DREADD） 已经成为多个项目的通用工具，并将成为大部分工作的一部分。的 DREADD技术基于G蛋白偶联受体的神经调节作用， 功能的神经元/电路控制，并已被证明是非常有效的探测电路功能 在动物模型中。该核心的服务将填补文献中的重大空白， 为INIA-Stress的许多项目提供援助。