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Influence of orbitofrontal cortex on mesolimbic dopamine and value-based choice.

眶额皮质对中脑边缘多巴胺和基于价值的选择的影响。

基本信息

批准号：
8715260
负责人：
Nick Garber Hollon
金额：
$ 3.33万
依托单位：
UNIVERSITY OF WASHINGTON
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：
2014-05-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8715260
关键词：
Affect Animals Area Behavior Behavior Control Behavioral Bilateral Choice Behavior Clozapine Complex Computer Simulation Conflict (Psychology)Cues Decision Making Designer Drugs Detection Direct Repeats Dopamine Dose Drug Addiction Expectancy Functional disorder GABA Agonists Gene Transfer Individual Investigation Learning Ligands Mediating Mental disorders Microinjections Midbrain structure Neurobiology Neurons Organism Outcome Oxides Pharmaceutical Preparations Physiology Play Procedures Process Psychological reinforcement Rattus Relative (related person)Research Rewards Role Satiation Scanning Signal Transduction Stimulus Substance Use Disorder System Techniques Testing Training Update Viral Work addiction base behavioral pharmacology design dopaminergic neuron drug of abuse drug reinforcement expectation experience flexibility innovation knowledge base motivated behavior novel preference psychostimulant public health relevance receptor reinforcer relating to nervous system research study success theories tool transmission process

项目摘要

DESCRIPTION (provided by applicant): The orbitofrontal cortex (OFC) and mesolimbic dopamine represent two neural substrates that are critical for adaptive motivated behavior, and their dysfunction has been implicated in the neuropathological mechanisms underlying substance use disorders. Neurons in both the OFC and the dopaminergic midbrain signal information related to learned values associated with reward-predicting stimuli, and both substrates are thereby thought to contribute to value-based decision making. Although each substrate may influence how the other stores and updates this value information, recent research has provided evidence of their distinct contributions to reward learning. Thus, investigations of the relative independence versus interactions of the OFC and mesolimbic dopamine function represent an open area of research that will enhance our understanding of the neurobiology underlying motivated behavior. The proposed studies aim to probe these circuit-level interactions by examining how perturbations of OFC activity affect mesolimbic dopamine transmission and value-based decision making. Toward this end, these experiments will employ a behavioral design adapted from a well-established tradition of animal learning theory and informed by recent advances in computational models of reinforcement learning. Additionally, this approach combines our lab's expertise in electrochemical detection techniques and my co-sponsor's novel viral tools for manipulating specific neuronal activity. After selectivel devaluing a previously reinforcing outcome and inactivating the OFC, I will record mesolimbic dopamine transmission using fast-scan cyclic voltammetry while rats perform a dual-reinforcer decision-making task. I will test the effects of OFC inactivation on the gradual updating of dopaminergic value signals and examine whether such dopamine release could contribute to the rats' decisions when the OFC is unavailable to flexibly guide behavioral choices. This inherently integrative and innovative approach will advance our understanding of valuation processes subserved by decision-making circuits whose normal function is disrupted in addiction.

描述（由申请人提供）：眶额皮质（OFC）和中脑边缘多巴胺代表了对适应性动机行为至关重要的两种神经基质，它们的功能障碍与物质使用障碍的神经病理学机制有关。OFC和多巴胺能中脑的神经元都发出与奖励预测刺激相关的学习值相关的信号信息，因此这两种底物都被认为有助于基于价值的决策。虽然每一种基质都可能影响另一种基质如何储存和更新这些价值信息，但最近的研究提供了它们对奖励学习的独特贡献的证据。因此，OFC和中脑边缘多巴胺功能的相对独立性与相互作用的研究代表了一个开放的研究领域，这将提高我们对动机行为背后的神经生物学的理解。拟议的研究旨在通过研究OFC活动的扰动如何影响中脑边缘多巴胺传输和基于价值的决策来探索这些回路水平的相互作用。为此，这些实验将采用一种行为设计，该设计改编自动物学习理论的成熟传统，并借鉴了强化学习计算模型的最新进展。此外，这种方法结合了我们实验室在电化学检测技术方面的专业知识和我的共同赞助者用于操纵特定神经元活动的新型病毒工具。在选择性地贬低先前强化的结果并使眶额皮层失活后，我将使用快速扫描循环伏安法记录大鼠执行双重决策任务时的中脑边缘多巴胺传递。我将测试OFC失活对多巴胺能价值信号逐渐更新的影响，并研究当OFC无法灵活指导行为选择时，这种多巴胺释放是否有助于大鼠的决策。这种内在的整合和创新方法将促进我们对决策回路所服务的评估过程的理解，这些决策回路的正常功能在成瘾中被破坏。