Role of prefrontostriatal circuits in effort-based, cost-benefit decision making

前额纹状体回路在基于努力的成本效益决策中的作用

基本信息

批准号：
10737578
负责人：
Scott Allen Wilke
金额：
$ 53.68万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-01 至 2028-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10737578
关键词：
Address Affective Animals Anterior Anxiety Behavior Behavioral Brain Characteristics Cognitive Corpus striatum structure Cost Analysis Costs and Benefits Data Decision Making Disease Disparate Dissociation Electrophysiology (science)Environment Evaluation Fiber Functional disorder Head Image Individual Intervention Learning Lesion Link Measurement Measures Mediating Mental Depression Mental disorders Methodology Microscope Mus Neurobiology Neurons Nucleus Accumbens Outcome Pathologic Patients Pattern Pharmacology Photometry Policies Population Dynamics Prefrontal Cortex Property Research Resolution Rewards Role Schizophrenia Signal Transduction Specificity Structure Substance Use Disorder Testing Therapeutic Intervention Translating Update Ventral Striatum addiction cell type cingulate cortex cost design excitatory neuron flexibility innovation miniaturize neural neural circuit neuromechanism novel optogenetics pharmacologic response spatiotemporal targeted treatment tool

项目摘要

PROJECT SUMMARY Ongoing evaluation of cost-benefit tradeoffs guides action selection during adaptive decision making. When outcomes change, the utility of potential actions is re-evaluated to determine whether to persist or deviate from an existing strategy. Disturbances in the neural mechanisms underlying cost-benefit decision making can lead to pathological behavior (e.g., addiction, OCD, depression/anxiety). Effort-based decision making is specifically disrupted in patients with depression, schizophrenia and substance use disorders. Although pathological behavior in these conditions is linked to dysfunction in the prefrontal cortex and striatum, we lack the detailed neurobiological understanding necessary to design targeted therapeutic interventions. We will address this deficit using cutting edge tools for measuring and manipulating neural activity in freely behaving animals. We will test the specific hypothesis that anterior cingulate cortex (ACC) to nucleus accumbens (NAc) projection neurons encode updates to action selection policies based on new effort-reward tradeoffs, and that inputs to the NAc instantiate new, effortful choice strategies. In Aim 1, we will use miniaturized head-mounted microscopes to determine how ACC and ACCàNAc projection neuron activity is organized to represent effort-related cost- benefit computations influencing action selection. In Aim 2, we will manipulate the activity of ACCàNAc projection neurons with optogenetics, during flexible decision making driven by changes in effort-related value. Finally, in Aim 3, we will focus on prefrontal projections to the NAc, measuring and inhibiting activity at ACCàNAc terminals and comparing with inputs from the orbitofrontal cortex (OFC). We will do this during decision making in the context of both effort and delay-costs as a tool to further refine our understanding of how NAc integrates prefrontal inputs and translates these into action selection. This proposal directly addresses a pressing need to understand the cell-type and circuit-specific mechanisms that mediate cost-benefit decision making. Our research can inform pharmacological, psychotherapeutic and brain stimulation interventions for a variety of psychiatric conditions characterized by disordered cost-benefit evaluations and decision making.

项目概要对成本效益权衡的持续评估指导适应性决策过程中的行动选择。结果发生变化，重新评估潜在行动的效用，以确定是坚持还是偏离现有策略的成本效益决策神经机制的紊乱可能会导致。病理行为（例如成瘾、强迫症、抑郁/焦虑）尤其如此。患有抑郁症、精神分裂症和药物滥用障碍的患者虽然是病理性的，但却受到干扰。这些情况下的行为与前额皮质和纹状体的功能障碍有关，我们缺乏详细的信息设计有针对性的治疗干预措施所必需的神经生物学理解我们将解决这一缺陷。我们将使用尖端工具来测量和操纵自由行为动物的神经活动。具体假设是前扣带皮层 (ACC) 到伏隔核 (NAc) 的投射神经元根据新的努力-回报权衡对行动选择策略进行编码更新，并将其输入到 NAc 在目标 1 中，我们将使用微型头戴式显微镜来实例化新的、有效的选择策略。确定 ACC 和 ACCàNAc 投影神经元活动如何组织来表示与努力相关的成本在目标 2 中，我们将操纵 ACCàNAc 的活动。在由努力相关价值的变化驱动的灵活决策过程中，具有光遗传学的投射神经元。最后，在目标 3 中，我们将重点关注前额叶对 NAc 的投射，测量和抑制 ACCàNAc 的活动我们将在决策过程中这样做。在努力和延迟成本的背景下，作为进一步完善我们对 NAc 如何集成的理解的工具该提案直接解决了前额输入并将其转化为行动选择的迫切需要。了解调节成本效益决策的细胞类型和电路特定机制。研究可以为各种药物、心理治疗和脑刺激干预措施提供信息以无序的成本效益评估和决策为特征的精神疾病。