Neurobiology of Social Behavior: Circuit Analysis in Early Life

社会行为的神经生物学：早期生活的回路分析

• 批准号: 10593708
• 负责人: Maya Opendak
• 金额: $ 5.8万
• 依托单位: HUGO W. MOSER RES INST KENNEDY KRIEGER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-20 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10593708
• 关键词: Age; Amygdaloid structure; Anxiety; Area; Award; Behavior; Behavioral; Biosensor; Brain; Complex; Coupling; Data; Development; Dopamine; Electrophysiology (science); Fiber; Goals; Grant; Growth; Individual; Infant; Infant Behavior; Latino; Lead; Life; Literature; Measures; Mediating; Mental disorders; Mentorship; Modeling; Neurobiology; Optics; Parents; Phase; Photometry; Plant Roots; Postdoctoral Fellow; Rattus; Research; Research Personnel; Resources; Schizophrenia; Signal Transduction; Social Behavior; Social Behavior Disorders; Structure; System; Technical Expertise; Techniques; Testing; Time; Training; Training Support; Virus; Work; autism spectrum disorder; career development; developmental neurobiology; dopaminergic neuron; effective therapy; flexibility; neural circuit; neurobehavioral; optogenetics; pup; recruit; relating to nervous system; skill acquisition; social; social bias

Project Summary For many species, access to resources requires a highly flexible system of social behavior that is sensitive to environmental demands. Indeed, inflexible social behavior can be highly maladaptive, particularly during developmental transitions when social demands are in constant flux. Yet, the neural substrates supporting flexible social behavior during development have been underexplored. The literature and pilot data collected for this proposal lead us to advance the central hypothesis that the basolateral amygdala (BLA) and its dopaminergic (DA) control are late-developing components of the social behavior circuit and their recruitment permits behavioral flexibility to transition a system biasing social approach within the nest into one favoring more inhibited approach as infants gain independence and enter the complex social world. Specifically, the goal of the parent BRAIN R00 Award is to apply advanced optical and electrophysiological techniques in infant rats to directly test this hypothesis in two specific aims. Aim 1 is to determine how adversity impacts electrophysiological signaling in the basolateral amygdala. Aim 2 will assess real-time dynamics of dopamine signaling within the BLA in typical and perturbed development. Aim 3 will examine the relationship between long-range VTA-BLA synchrony and social approach by optogenetically manipulating DA neurons in the VTA of rats performing a social behavior task while recording spike-LFP synchrony in the VTA and the BLA. Lack of understanding of the developmental neurobiology underlying social behavior disorders impedes our search for effective therapies. By integrating advanced functional techniques into the study of complex infant behavior, the proposed work will advance the field both technically and conceptually. To pursue these Aims, we are requesting this supplement to support the training and career development of a postdoctoral researcher, Dr. Cesar Medina. Dr. Medina is a Latino U.S. citizen. He will be working as a postdoctoral fellow in my lab to model adversity and collect neurobehavioral measures during rat pup social behavior at these two ages. In support of Aim 2 of the parent R00 grant, Dr. Medina will employ virus-mediated strategies to measure the activity of biosensors for dopamine in the basolateral amygdala using fiber photometry. In support of Aim 3, Dr. Medina will record from multiple brain areas simultaneously and assess measures of functional coupling between spikes and oscillations (local field potentials, LFP), including synchrony, coherence, power, directional entrainment, and phase-phase coupling. During the proposed support period, Dr. Medina will receive training in technical skills and career development from Dr. Maya Opendak and Dr. Jeremiah Cohen. This training and mentorship will be structured to support Dr. Medina’s goal of leading an independent research team studying the neural circuitry supporting complex behavior and how it is impacted by adversity.

项目摘要 对于许多物种来说，获取资源需要高度灵活的社会行为系统，这是敏感的 对环境的要求。事实上，僵化的社会行为可能非常不适应，特别是在 当社会需求不断变化时的发展转型。然而，支持的神经底物 在发展过程中灵活的社会行为一直没有得到充分的研究。为以下目的收集的文献和试点数据 这一建议使我们提出了杏仁基底外侧核(BLA)及其 多巴胺能(DA)控制是社会行为回路及其招募的晚期组成部分 允许行为灵活性，将巢内偏向系统的社交方式转变为更倾向于 当婴儿获得独立并进入复杂的社会世界时，受抑制的方法。具体地说， 亲脑R00奖是将先进的光学和电生理技术应用于幼年大鼠 直接在两个具体目标上检验这一假设。目标1是确定逆境如何影响电生理 杏仁基底外侧核的信号。目标2将评估多巴胺信号的实时动态 血乳酸处于典型的和不安的发展中。目标3将研究长程VTA-BLA之间的关系 光遗传操作大鼠VTA中DA神经元的同步性和社会性方法 社会行为任务，同时记录VTA和BLA中的峰-LFP同步。对这一问题缺乏了解 社会行为障碍背后的发育神经生物学阻碍了我们寻找有效的治疗方法。通过 将先进的功能技术整合到复杂婴儿行为的研究中，拟议的工作将 在技术和概念上推进这一领域。 为了实现这些目标，我们请求这一补充，以支持以下人员的培训和职业发展 博士后研究员塞萨尔·梅迪纳博士。梅迪纳博士是一名拉丁裔美国公民。他将作为一名 我实验室的博士后研究员，在老鼠幼崽社交期间建立逆境模型并收集神经行为测量数据 在这两个年龄段的行为。为了支持父母R00资助的Aim 2，麦迪纳博士将使用病毒介导的方法 使用纤维光度法测量杏仁基底外侧核多巴胺生物传感器活性的策略。 为了支持目标3，梅迪纳博士将同时从多个大脑区域进行记录，并评估 尖峰和振荡之间的功能耦合(局部场势，LFP)，包括同步，相干， 功率、定向夹带和相-相耦合。在拟议的支持期内，麦迪纳博士将 从玛雅·奥本达克博士和耶利米·科恩博士那里接受技术技能和职业发展方面的培训。 这种培训和指导的结构将支持麦迪纳博士领导一项独立研究的目标 团队研究支持复杂行为的神经回路以及它如何受到逆境的影响。