Accumbens neuronal subtypes in addiction

成瘾中的伏隔神经元亚型

基本信息

批准号：
8846089
负责人：
Lucas L Sjulson
金额：
$ 18.05万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-06-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8846089
关键词：
Accounting Affect Amygdaloid structure Animal Behavior Animal Genetics Animals Behavior Behavioral Behavioral Assay Behavioral Genetics Behavioral Model Behavioral Paradigm Brain Brain Part Brain region Cells Cocaine Cocaine Dependence Collaborations Complement Complex Cues Data Designer Drugs Development Disease Extinction (Psychology)Face Functional disorder Future Goals Hand Health Hippocampus (Brain)Interneurons Knowledge Laboratories Lead Light Maps Measures Medial Mediating Minor Modeling Monitor Mus Neocortex Neurobiology Neurons Nucleus Accumbens Parvalbumins Pathogenesis Pattern Pharmaceutical Preparations Physiological Play Population Property Prosencephalon Relapse Reporting Research Research Project Grants Research Proposals Rodent Role Self Administration Somatostatin Structure Techniques Testing Therapeutic Training Training Activity Transgenic Mice Transgenic Organisms Tyrosine 3-Monooxygenase addiction behavior test calretinin cell type cholinergic design experience genetic approach improved in vivo neuronal patterning neurophysiology neuropsychiatry new therapeutic target novel operation optogenetics preference programs receptor receptor expression recombinase relating to nervous system research study skills

项目摘要

DESCRIPTION (provided by applicant): My long-term goal is to establish an independent research program aimed at investigating the underlying pathophysiology of addictive disorders and using this information to guide development of novel treatments. To accomplish this, I plan to model cocaine addiction in rodents and use a combination of genetic, behavioral, and neurophysiological techniques to determine underlying mechanisms and identify candidate therapeutic strategies. The immediate goal of this research proposal is to determine the physiological firing patterns and functional importance of GABAergic interneurons of the nucleus accumbens in addiction-related behaviors such as cocaine conditioned place preference and cocaine self-administration with cue-induced reinstatement. To complement my prior experience with animal behavior and genetic approaches for targeted manipulation of neural activity, the training plan contains several major components. The first of these includes formal training in complex behavioral models of addiction and in vivo neurophysiology/optogenetics techniques used to monitor neuronal activity of specific interneuron types in behaving animals. These training components are necessary not only to carry out the research plan as proposed, but also as skills required for future studies in my own independent laboratory. This will be complemented by training aims designed to expand my knowledge of general neurophysiology and the neurobiology of addiction, as well as a training aim designed to prepare me for practical aspects of laboratory management. Research Project Description: The nucleus accumbens (NAc) is a brain region known to be central to the pathophysiology of cocaine addiction, but its internal operations are poorly understood. Investigating these mechanisms requires studying the NAc at the level of each of its constituent neuronal subtypes. GABAergic interneurons (gINs) represent the subtype of neuron in the NAc that is perhaps most poorly understood in the context of addiction, despite the fact that these cells play key functional roles in other parts of the brain and are thought to be affected in multiple neuropsychiatric disorders. We first propose to test the hypothesis that identified gIN populations in the NAc play important functional roles i addiction-related behaviors by manipulating activity in each of the major gIN subclasses and measuring the effect on mouse behavioral models of cocaine addiction and relapse. We additionally propose to gain further understanding of gIN function by recording neuronal activity from gINs during addiction-related behaviors. These studies will advance our understanding of NAc function in addiction and may lead to the identification of novel therapeutic targets. Title of proposal: Functional roles of GABAergic interneurons of the nucleus accumbens in cocaine addiction Specific Aims: Aim 1: To test the hypothesis that identified GABAergic interneuron subpopulations in the medial nucleus accumbens shell play functional roles in context-dependent cocaine addiction-related behaviors Aim 2: To determine the physiological firing patterns of each GABAergic interneuron subpopulation in the nucleus accumbens during cocaine self-administration, extinction, and context-induced reinstatement

描述（由申请人提供）：我的长期目标是建立一个独立的研究计划，旨在研究成瘾性疾病的潜在病理生理学，并使用这些信息来指导新疗法的发展。为此，我计划在啮齿动物中对可卡因成瘾进行建模，并结合遗传，行为和神经生理技术来确定基本机制并确定候选治疗策略。该研究提案的直接目标是确定伏伏核中GABA能中神经元在成瘾相关行为中的生理发射模式和功能重要性，例如可卡因条件调节的位置偏好和可卡因的自我管理，并通过提示引起的恢复。为了补充我对动物行为和遗传方法的先前经验，以靶向对神经活动的有针对性操纵，培训计划包含几个主要组成部分。其中的第一个包括在成瘾的复杂行为模型和体内神经生理学/光遗传学技术中进行的正式培训，用于监测特定的中间神经元类型的神经元活性。这些培训组件不仅需要按照提出的研究计划，而且是我自己独立实验室中未来研究所需的技能。培训目标将补充这一点，旨在扩大我对一般神经生理学和成瘾神经生物学的了解，以及旨在为我为实验室管理的实际方面做好准备的培训目标。研究项目描述：伏隔核（NAC）是一个大脑区域，已知是可卡因成瘾的病理生理学的核心，但其内部操作知之甚少。研究这些机制需要在其每个组成神经元亚型的水平上研究NAC。 GABA能中间神经元（GINS）代表NAC中神经元的亚型，尽管这些细胞在成瘾的背景下也许最糟糕的是，这些细胞在其他部分中在其他部分中起关键功能作用大脑被认为受到多种神经精神疾病的影响。我们首先建议测试NAC中确定的杜松子酒种群通过操纵每个主要杜松子群中的活动并衡量对可卡因成瘾和复发的小鼠行为模型的影响的假设。我们还建议通过记录与成瘾相关行为期间杜松子的神经元活性来进一步了解杜松子酒功能。这些研究将提高我们对成瘾中NAC功能的理解，并可能导致对新型治疗靶标的识别。标题提议：可卡因成瘾中的核核中GABA能中间神经元的功能作用，目的1：测试以下假说，该假说鉴定出gabaergic的中间核中间核中的核核中壳中的壳中的壳中的壳中的壳在上下文中依赖于上下文依赖的可卡因成瘾性行为的作用在上下文中扮演着依赖于情境的性行为2：可卡因自我给药，灭绝和上下文诱导的恢复原状期间，伏隔核的亚群