Neurobiology of Social Behavior: Circuit Analysis in Early Life

项目摘要 我的长期职业目标是建立一个研究实验室，解剖功能微电路， 典型和扰动发展中的灵活社会行为。实验室将整合最先进的技术 一个大型的收敛方法工具包，以评估神经网络如何表现出可塑性， 早期的适应行为为了有效地领导这个未来的研究团队，我需要额外的专业人员 发展和培训技术，以测量和操纵行为婴儿的神经功能。我 迄今为止的培训为我提供了啮齿动物发育神经生物学，压力， 电生理学、光遗传学和离体成像技术以及广泛的理论方法。我的职业生涯 发展计划通过专业发展活动和光纤培训扩展了这一技能 光度测定和使用微驱动器来评估行为期间的神经回路动态。通过参与这个 在有保障的培训时间内，我将为进入我的独立研究阶段做好充分的准备，带领一个研究团队 旨在揭示支持社会行为的神经回路的可塑性。研究项目：对于许多 物种，获取资源需要高度灵活的社会行为系统，对环境敏感， 要求。事实上，僵化的社会行为可能是高度适应不良的，特别是在发展过程中。 当社会需求不断变化时，然而，支持灵活社交的神经基质 发育过程中的行为还未被充分研究。为该提案收集的文献和试点数据 这使我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的后期发展组成部分，它们的招募允许行为 灵活性，将巢内偏向社会的系统转变为偏向更受抑制的系统 当婴儿获得独立并进入复杂的社会世界时，具体来说，这个大脑的目标是 K99-R 00奖是将先进的光学和电生理技术应用于幼年大鼠， 这一假设有三个具体目标。目标1将在辅导阶段（K99）执行， 确定在发展中，社交方式何时受到抑制，以及BLA如何控制。目的 2，在辅导阶段（K99）开始，在独立阶段（R 00）完成， VTA DA释放到BLA在使用会聚方法操纵的社会方法抑制中的作用 测量血脑屏障中多巴胺的含量在独立阶段（R 00）执行的目标3将检查 通过光遗传学操纵DA研究VTA-BLA长距离同步性与社会接近的关系 大鼠腹侧被盖区的神经元执行社会行为任务，同时记录腹侧被盖区的锋电位-LFP同步 还有BLA对社会行为障碍背后的发育神经生物学缺乏了解 阻碍了我们寻找有效的治疗方法通过将先进的功能性技术整合到 复杂的婴儿行为，拟议的工作将推进该领域的技术和概念。

Project Summary My long-termcareer goal is to establish a research laboratory that dissects functional microcircuits supporting flexible social behavior in typical and perturbed development. The lab will integrate state-of-the-art techniques into a large toolkit of convergent methodologies to assess how neural networks exhibit plasticity to support adaptive behavior in early life. To effectively lead this future research team, I require additional professional development and training in techniques for measuring and manipulating neural function in behaving infants. My training to date has provided me with a strong foundation of skills in rodent developmental neurobiology, stress, electrophysiology, optogenetics and ex vivo imaging techniques and a broad theoretical approach. My career development plan expands on this skill set with professional development activities and training in fiber photometry and the use of microdrives to assess neural circuit dynamics during behavior. By engaging in this protected training time, I will enter my independent stage of research well-prepared to lead a research team established to uncover the plasticity of neural circuits supporting social behavior. Research Project: For many species, access to resources requiresa 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 leads me 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 socia l world. Specifically, the goal of this BRAIN K99-R00 Award is to apply advanced optical and electrophysiological techniques in infant rats to directly test this hypothesis in three specific aims. Aim 1 will be performed during the mentored phase (K99) and is to determine when in development social approach becomes inhibited and how this is controlled by the BLA. Aim 2, initiated during the mentored phase (K99) and completed duringthe independent phase (R00), is to determine the role of VTA DA release into the BLA in social approach inhibition using convergent approaches to manipulate and measure DA levels in the BLA. Aim 3, performed during the independent phase (R00), 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.