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.

项目概要 对于许多物种来说，获取资源需要高度灵活、敏感的社会行为系统 以适应环保要求。事实上，不灵活的社会行为可能会导致高度适应不良，尤其是在 当社会需求不断变化时，就会发生发展转变。然而，支持的神经基质 发育过程中灵活的社会行为尚未得到充分探索。收集的文献和试点数据 这个提议引导我们提出了一个中心假设：基底外侧杏仁核（BLA）及其 多巴胺能 (DA) 控制是社会行为回路及其招募的晚期发展组成部分 允许行为灵活性，将巢内有偏见的社会方法转变为有利于更多人的社会方法 当婴儿获得独立并进入复杂的社交世界时，他们的方法会受到抑制。具体来说，目标是 BRAIN R00 母奖旨在将先进的光学和电生理技术应用于幼年大鼠， 在两个特定目标中直接检验该假设。目标 1 是确定逆境如何影响电生理 基底外侧杏仁核中的信号传导。目标 2 将评估多巴胺信号传导的实时动态 BLA 处于典型和扰动的发展状态。目标 3 将检查远程 VTA-BLA 之间的关系 通过光遗传学操作大鼠 VTA 中的 DA 神经元进行同步和社会方法 社会行为任务，同时记录 VTA 和 BLA 中的尖峰 LFP 同步。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。经过 将先进的功能技术融入复杂婴儿行为的研究中，拟议的工作将 在技​​术和概念上推进该领域。 为了实现这些目标，我们要求提供此补充材料以支持培训和职业发展 博士后研究员 Cesar Medina 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模拟逆境并收集大鼠幼崽社交期间的神经行为测量 这两个年龄段的行为。为了支持 R00 母基金的目标 2，Medina 博士将采用病毒介导的方法 使用光纤光度测定法测量基底外侧杏仁核中多巴胺生物传感器活性的策略。 为了支持目标 3，梅迪纳博士将同时记录多个大脑区域并评估 尖峰和振荡之间的功能耦合（局部场电位，LFP），包括同步性、相干性、 功率、方向夹带和相间耦合。在提议的支持期内，Medina 博士将 接受 Maya Opendak 博士和 Jeremiah Cohen 博士的技术技能和职业发展培训。 这种培训和指导将旨在支持梅迪纳博士领导独立研究的目标 团队研究支持复杂行为的神经回路及其如何受到逆境的影响。