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

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

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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.

项目摘要对成本效益折衷方案的持续评估指导自适应决策过程中的行动选择。什么时候结果发生了变化，重新评估潜在行动的实用性，以确定是持续还是偏离现有的策略。基于成本效益决策的神经机制的干扰可能会导致病理行为（例如成瘾，强迫症，抑郁/焦虑）。基于努力的决策是专门的抑郁症，精神分裂症和药物使用障碍的患者中断。虽然病理在这些条件下的行为与前额叶皮层和纹状体中的功能障碍有关，我们缺乏细节设计有针对性的治疗干预所必需的神经生物学理解。我们将解决这个辩护使用尖端工具来测量和操纵自由表现动物的神经活动。我们将测试伏隔核（NAC）投射神经元前扣带回皮质（ACC）的特定假设编码基于新的努力折衷方案的行动选择策略的更新，并输入NAC 实例化新的，努力的选择策略。在AIM 1中，我们将使用微型的头部安装显微镜确定如何组织ACC和ACCàNAC投射神经元活动以表示与努力相关的成本 - 利益计算会影响行动选择。在AIM 2中，我们将操纵Accànac的活动具有光遗传学的投影神经元，在柔性决策过程中通过与努力相关的值的变化进行动力。最后，在AIM 3中，我们将专注于NAC的前额叶预测，测量和抑制Accànac的活动终端和与Orbitrontal Cortex（OFC）的输入进行比较。我们将在决策过程中这样做在努力和延迟成本的背景下，作为一种工具，可以进一步完善我们对NAC如何整合的理解前额叶输入并将其转化为行动选择。该建议直接解决了紧迫的需求了解介导成本效益决策的细胞类型和电路特异性机制。我们的研究可以为药物，心理治疗和大脑刺激干预提供信息以成本效益评估和决策为特征的精神病疾病。