Decoding ensemble dynamics from cortico-amygdalar circuits during social choice

在社会选择过程中从皮质-杏仁核回路解码整体动态

• 批准号: 10723932
• 负责人: AZA Stephen Allsop
• 金额: $ 19.24万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2028-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723932
• 关键词: Absence of pain sensation; Acute; Algorithms; Amygdaloid structure; Animals; Anterior; Bayesian Modeling; Behavior; Behavioral; Behavioral Model; Behavioral Paradigm; Clinical; Computer Models; Computing Methodologies; Data; Decision Making; Dimensions; Empathy; Environment; FDA approved; Feeling; Goals; Health; Human; Impairment; Intervention; Joints; K-Series Research Career Programs; Machine Learning; Measures; Mediator; Mentors; Methamphetamine; Methods; Mus; Neurons; Neurosciences; Nonlinear Dynamics; Nucleus Accumbens; Pain; Partner in relationship; Pharmaceutical Preparations; Post-Traumatic Stress Disorders; Primates; Research; Research Personnel; Rewards; Rodent; Role; Social Behavior; Social Change; Social Environment; Social Interaction; Social Processes; Space Models; Statistical Models; Stimulus; Stress; Structure; Subgroup; System; Testing; Training; behavioral pharmacology; career; cingulate cortex; clinically significant; deep learning; deep learning model; ecstasy; experience; experimental study; individual variation; innovation; neural; neural circuit; neural model; neuromechanism; neuronal circuitry; neuropsychiatry; neurotransmission; novel; optogenetics; pharmacologic; preference; response; skills; social; social anxiety; social bias; social cognition; social learning; social relationships; tool; vector

Project Summary Social relationships are a key component of human health and survival and impairments in social behavior have a major impact in many psychiatric conditions. Yet despite the importance of social context to health, there remains no FDA-approved medications that target social cognition and behavior. Social context is defined by the social stimuli available to an animal, is a key mediator of behavior in rodents, and impacts social choices. Yet little is known about how neuronal circuits encode social context and choice.In rodents, circuits in ACC that project to the amygdala (ACC- BLA) and Nucleus accumbens (ACC-Nac) have been shown to be necessary for different aspects of social information transfer. However, how neural activity in these regions encode social context and choice is not known. We developed a social choice paradigm in which mice choose access to a novel or a familiar/cagemate mouse. In this novel paradigm, mice consistently show preference for a social target over a novel object, but they show variable individual biases in social choice between a novel and cagemate conspecific. Recording neural activity from the ACC-BLA and ACC-Nac circuits during this behavioral paradigm will allow for a more nuanced understanding of the neural mechanisms underlying social choice. In order to better understand how activity recorded during this and traditional social behavioral paradigms we will leverage recently developed statistical models and inference algorithms to cluster nonlinear dynamical neural responses into an unspecified number of functional sub-groups called Functional Encoding Units (FEUs). We will also apply deep learning tools for behavioral analysis to engage in joint modeling of neural and behavioral data. This will enhance our ability to predict social context and enrich encoding of social behavior. Lastly, given the impact of 3,4-Methylenedioxy methamphetamine (MDMA) on social behavior and empathy and its recent clinical significance in post traumatic stress disorder, we hypothesize that MDMA paired social exposure will bias social choice in our paradigm. We will apply deep learning to behavioral analysis of our paradigm in order to test this hypothesis. Through this K-Award we will define how social stimuli are encoded in a context-specific manner within ACC-BLA and ACC-Nac circuits during social choice and how MDMA biases these social choices. In parallel, intensive mentoring, directed readings, and structured coursework will enhance my skills and toolkit in computational modeling and machine learning-based analysis of both neural and behavioral data, and behavioral pharmacology, setting the stage for independence.

项目概要 社会关系是人类健康和生存的重要组成部分，也是社会关系的障碍 行为对许多精神疾病有重大影响。然而，尽管社交很重要 就健康而言，目前尚无 FDA 批准的针对社会认知和 行为。社会环境是由动物可获得的社会刺激定义的，是一个关键的中介因素 啮齿动物的行为，并影响社会选择。然而，人们对神经元回路如何运作知之甚少。 编码社会背景和选择。在啮齿类动物中，ACC 中的电路投射到杏仁核（ACC- BLA) 和伏隔核 (ACC-Nac) 已被证明对于不同方面都是必要的 社会信息传递。然而，这些区域的神经活动如何编码社会背景 和选择是未知的。我们开发了一种社会选择范式，其中小鼠选择访问 小说或熟悉的/笼中的老鼠。在这个新颖的范例中，小鼠始终表现出 对社会目标的偏好超过新奇的对象，但他们在社会方面表现出不同的个人偏见 在小说和笼友同种之间进行选择。从 ACC-BLA 记录神经活动 和 ACC-Nac 电路在此行为范式中将允许更细致的 了解社会选择背后的神经机制。为了更好地理解 我们将如何利用在此期间记录的活动以及传统的社会行为范式 最近开发了统计模型和推理算法来聚类非线性动态 将神经反应转化为未指定数量的功能子组，称为功能编码 单位 (FEU)。我们还将应用深度学习工具进行行为分析，共同参与 神经和行为数据建模。这将增强我们预测社会背景和 丰富社会行为的编码。最后，考虑到 3,4-亚甲二氧基的影响 甲基苯丙胺（MDMA）对社会行为和同理心的影响及其近期临床意义 创伤后应激障碍，我们假设 MDMA 配对的社交暴露会使社交产生偏见 我们范式中的选择。我们将把深度学习应用到我们范式的行为分析中 为了检验这个假设。通过这个 K 奖，我们将定义社交刺激的编码方式 在社会选择过程中，在 ACC-BLA 和 ACC-Nac 回路中以特定情境的方式进行 MDMA 使这些社会选择产生偏见。同时，强化指导、定向阅读和 结构化课程将增强我在计算建模和机器方面的技能和工具包 基于学习的神经和行为数据分析以及行为药理学、设置 独立的舞台。