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 对许多物种来说，获取资源需要一个高度灵活的社会行为系统，这个系统是敏感的 环境需求。事实上，僵化的社会行为可能是高度适应不良的，特别是在 社会需求不断变化时的发展转型。然而，神经基质支持 在发育过程中灵活的社会行为还未被充分探索。收集的文献和试点数据， 这一提议使我们提出了一个中心假设，即基底外侧杏仁核（BLA）及其 多巴胺能（DA）控制是社会行为回路及其募集的晚期发育成分 允许行为灵活性，将巢内偏向社会的系统方法转变为偏向更多的社会方法， 当婴儿获得独立并进入复杂的社会世界时，具体而言，目标是 父母脑R00奖是应用先进的光学和电生理技术在婴儿大鼠， 在两个具体目标中直接检验这一假设。目的1是确定逆境如何影响电生理 基底外侧杏仁核的信号。Aim 2将评估多巴胺信号在脑内的实时动态。 BLA在典型和扰动发展。目标3将研究远程VTA-BLA之间的关系 通过光遗传学操纵大鼠腹侧被盖区的DA神经元， 社交行为任务，同时记录VTA和BLA中的尖峰-LFP同步。不了解 发展神经生物学基础的社会行为障碍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的婴儿行为研究中， 在技术上和概念上推进这一领域。 为了实现这些目标，我们要求提供这一补充，以支持以下人员的培训和职业发展： 博士后研究员塞萨尔·梅迪纳博士梅迪纳医生是拉丁裔美国公民。他将作为一名 在我的实验室里，我是一名博士后，在老鼠幼崽的社交过程中， 这两个年龄段的行为。为了支持父R00赠款的目标2，麦地那博士将采用病毒介导的 策略，以衡量活动的生物传感器多巴胺在基底外侧杏仁核使用纤维光度法。 为了支持目标3，Medina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、定向夹带和相-相耦合。在拟议的支持期间，麦地那博士将 接受Maya Opendak博士和Jeremiah Cohen博士的技术技能和职业发展培训。 这种培训和指导将结构，以支持麦地那博士的目标，领导一个独立的研究 研究支持复杂行为的神经回路以及逆境如何影响神经回路的团队。