Neuronal ensembles in extinction of cocaine seeking.

可卡因寻求消失的神经元群。

• 批准号: 10087744
• 负责人: Brandon L Warren
• 金额: $ 9.26万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-02-01 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10087744
• 关键词: Amygdaloid structure; Animal Model; Appetitive Behavior; Area; Award; Behavior; Behavioral Model; Behavioral Research; Brain; Brain region; Cessation of life; Cocaine; Cocaine Dependence; Cues; Disease; Drug Addiction; Drug abuse; Extinction (Psychology); Functional disorder; Goals; Grant; Halorhodopsins; Individual; Label; Learning; Lesion; Measures; Medial; Mediating; Memory; Mental disorders; Mentors; Mentorship; Methodology; Methods; Motivation; Neurobiology; Neurons; Nucleus Accumbens; Outcome; Pathway interactions; Pattern; Pharmaceutical Preparations; Phase; Post-Traumatic Stress Disorders; Prefrontal Cortex; Public Health; Rattus; Research; Research Personnel; Role; Self Administration; System; Testing; Tetanus Helper Peptide; Thinking; Training; Transgenic Organisms; United States; Virus; addiction; base; conditioned fear; design; drug craving; drug relapse; effective therapy; experimental study; immunoreactivity; in vivo; insight; learning extinction; neural circuit; novel; optogenetics; programs; prospective; reinforcer; therapeutic target; tool

Project summary/abstract Cocaine addiction is a multidimensional psychiatric disorder with pathophysiology that seems to involve abnormally strong learned associations. These types of learned associations are thought to be encoding within patterns of sparsely distributed neurons, called neuronal ensembles. During the last decade, research has mostly focused on acquisition and reinstatement of cocaine seeking. However, cocaine self-administration can be rapidly extinguished by omitting the cocaine reinforcer. This extinction learning appears to involve formation of a new memory, rather than an `unlearning' of self-administration because extinguished behaviors can reinstate. Relatively few studies have attempted to delineate the neurobiological underpinnings of extinction of cocaine seeking. Under the primary mentorship of Drs. Bruce Hope and Yavin Shaham, the present Pathway to Independence award will allow me to obtain training in optogenetic and transgenic methodologies that will allow me to probe the role of neuronal ensembles in extinction learning. In the mentored phase of this grant, I will use double transgenic fos-tet-cre rats to label neuronal ensembles associated with self-administration and extinction of cocaine seeking separately. I will design and build an optogenetics system that will then allow me to inhibit these distinct ensembles in vivo in behaving rats to show necessity of neuronal ensembles in extinction of cocaine seeking. In the independent phase, I will determine whether these self-administration and extinction ensembles project to distinct brain regions. I will then use optogenetics methodologies mastered in the mentored phase to inhibit these projections to determine whether the projections are necessary for inhibition of cocaine seeking following extinction of cocaine seeking. Under the mentorship of Drs. Hope and Shaham, I am uniquely situated to combine Dr. Hope's expertise on neuronal ensemble-level manipulations with Dr. Shaham's expertise on behavioral models of drug addiction in an academic setting focused on studying drug addiction. Thus, this proposal will provide novel insights on an understudied, but fundamental aspect of motivation while preparing me to thrive as an independent investigator. Simultaneously, this award will provide me with the tools necessary to establish an independent research program capable of producing high-impact research combining cutting edge neuronal ensemble methods with behavioral models of drug addiction.

项目概要/摘要 可卡因成瘾是一种多维度的精神疾病，其病理生理学似乎涉及 异常强烈的习得性联想。这些类型的习得性联想被认为是编码在 稀疏分布的神经元的模式，称为神经元集合。在过去的十年里，研究 主要集中在可卡因寻求的获得和恢复。然而，可卡因自我管理可以 可以通过省略可卡因消除剂而迅速消除。这种灭绝学习似乎涉及形成 一个新的记忆，而不是一个“遗忘”的自我管理，因为熄灭的行为可以 复职相对较少的研究试图描绘灭绝的神经生物学基础， 寻找可卡因在布鲁斯霍普博士和雅文沙哈姆博士的主要指导下，目前的通往 独立奖将使我能够获得光遗传学和转基因方法学方面的培训， 探索神经元集合在消退学习中的作用。在本补助金的指导阶段，我将使用 双转基因fos-tet-cre大鼠标记与自我给药和消退相关的神经元系综 单独寻找可卡因。我将设计并建造一个光遗传学系统， 这些不同的合奏在体内的行为大鼠，以显示必要的神经元合奏的灭绝， 寻找可卡因在独立阶段，我将决定这些是否自我管理和灭绝 合奏投射到不同的大脑区域。然后，我将使用光遗传学方法学掌握在 指导阶段，以抑制这些预测，以确定预测是否是必要的抑制 寻求可卡因的行为消失后，寻求可卡因的行为也随之消失。在霍普博士和沙汉姆博士的指导下， 独特的位置，结合联合收割机博士希望的专业知识，神经元整体水平的操作与博士沙哈姆的 在专注于研究药物成瘾的学术环境中提供药物成瘾行为模型方面的专业知识。 因此，这一建议将提供一个未充分研究的新见解，但动机的基本方面， 让我成为一名独立调查员同时，这个奖项将为我提供工具 有必要建立一个独立的研究计划，能够产生高影响力的研究结合 尖端神经元集成方法与药物成瘾行为模型。