Amygdala-cortical circuitry in reward encoding, expectation, and decision making

奖励编码、期望和决策中的杏仁核皮质回路

基本信息

批准号：
10318940
负责人：
Kate M Wassum
金额：
$ 36.69万
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：
2019
资助国家：
美国
起止时间：
2019-02-15 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10318940
关键词：
Accounting Ache Adaptive Behaviors Address Amygdaloid structure Anatomy Anxiety Association Learning Back Behavior Behavioral Brain Brain region Calcium Cells Crime Cues Data Decision Making Diagnosis Emotional Event Exposure to Failure Fiber Functional disorder Funding Future Genetic Recombination Goals Healthcare Human Imprisonment Individual Information Distribution Information Retrieval Investigation Lateral Law Enforcement Learning Link Measurement Medial Mediating Memory Mental Depression Mental disorders Monitor Neurobehavioral Manifestations Neurons Outcome Pathologic Patients Photometry Plant Roots Population Procedures Process Psyche structure Public Health Research Retrieval Rewards Rodent Schizophrenia Stimulus Symptoms System Techniques Testing Therapeutic Intervention Work addiction base behavior test calcium indicator cell type classical conditioning combat comorbidity cost defined contribution expectation experience genetic manipulation innovation insight memory encoding memory retrieval neural circuit nonhuman primate optogenetics prevent prospective relating to nervous system simulation theories therapeutic target

项目摘要

PROJECT SUMMARY Growing evidence suggests that the cognitive symptoms underlying many psychiatric disorders, including addiction, result from a failure to appropriately learn about and/or anticipate potential future events. Indeed, deficits in the prospective consideration of potential rewarding events have been detected in patients diagnosed with addiction, accounting for their inability to limit use despite deleterious consequences. Similar deficits have been identified in patients diagnosed with mental illnesses comorbid with addiction, such as depression, anxiety, and schizophrenia. These mental illnesses are major intractable public health problems in the US, accounting for hundreds of billions of dollars in costs associated with health care, crime, incarceration and law enforcement. Effective approaches to prevent and/or treat these conditions are, therefore, badly needed. The goal of this research is to expose the neural circuits required to learn predictive relationships and to use this information to generate expectations about the future, in order to gain insight into how pathological states arise and determine what can be done to combat them. Addictive substances are thought to hijack the brain systems that normally support adaptive decision making, resulting in maladaptive choices. Adaptive decision making requires accurate prospective consideration of possible future events. Prior encoding of specific stimulus-reward associative memories enables this prospective consideration by allowing the mental simulation (i.e., representation) of possible future rewarding events. Recent studies in rodents and humans have indicated that the basolateral amygdala (BLA) might be a brain region crucial for learning these associations, but precisely how and the neural circuitry through which it achives this function are unknown. The proposed research provides a critical, in-depth, and hypothesis-driven investigation of the contribution of the BLA and its reciprocal connections with the orbitofrontal cortex, a region implicated in decision making, to stimulus-reward encoding and subsequent retrieval of this information to guide adaptive behavior and choice. This will be achieved through a multi-faceted and integrative neural recording and manipulation approach. We will combine projection-specific activity monitoring, tag and capture techniques for manipulation of specific event-activated neuronal ensembles, and behavioral procedures with translational relevance to symptoms of human mental illness to uncover the function of amgydala-cortical loops in adaptive reward-guided behavior and decision making.

项目摘要越来越多的证据表明，许多精神疾病的认知症状，包括成瘾是由于未能适当学习和/或预期潜在的未来事件而导致的。的确，在被诊断的患者中发现了潜在奖励事件的预期考虑的缺陷随着成瘾，尽管后果有害，但他们仍无法限制使用。类似的赤字也有在被诊断出患有抑郁症，焦虑，焦虑，和精神分裂症。这些精神疾病在美国是主要棘手的公共卫生问题，会计与医疗保健，犯罪，监禁和执法相关的数百亿美元的费用。因此，急需预防和/或治疗这些疾病的有效方法是急需的。目标的目标研究是揭示学习预测关系所需的神经回路，并使用此信息来产生对未来的期望，以深入了解病理状态的出现并确定可以采取什么措施来对抗他们。人们认为上瘾的物质劫持了通常支持自适应决策的大脑系统导致适应不良的选择。自适应决策需要准确考虑可能的未来事件。事先编码特定的刺激 - 奖励联想记忆可以实现这一前瞻性通过允许对未来奖励事件的心理模拟（即表示）进行考虑。最近的对啮齿动物和人类的研究表明，基底外侧杏仁核（BLA）可能是大脑区域对于学习这些关联至关重要，但正是如何实现这一目标的神经电路和神经电路功能未知。拟议的研究提供了一个关键，深入和假设驱动的研究 BLA及其与Orbitrontal皮层的相互连接的贡献，该区域涉及决策，以刺激奖励编码和随后检索此信息以指导自适应行为和选择。这将通过多方面的综合神经记录来实现操纵方法。我们将结合特定于投影的活动监视，标记和捕获技术操纵特定事件激活的神经元集合和具有翻译的行为程序与人类精神疾病的症状相关，以发现自适应中Amgydala皮层环的功能奖励指导的行为和决策。