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，解剖功能微电路支持 典型心烦意乱发展中的灵活社会行为。该实验室将整合最先进的技术 集成到融合方法的大型工具包中，以评估神经网络如何表现出支持的可塑性 早期生活中的适应性行为。为了有效地领导这个未来的研究团队，我需要更多的专业人员 开发和培训测量和操作行为正常婴儿神经功能的技术。我的 到目前为止，培训为我提供了坚实的啮齿动物发育神经生物学、压力、 电生理学、光遗传学和体外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来扩展这一技能集 光度学和使用微驱动器来评估行为过程中的神经回路动力学。通过从事这项工作 保护训练的时间，我将进入我的独立研究阶段，为带领一个研究团队做好准备 旨在揭示支持社会行为的神经回路的可塑性。研究项目：对许多人来说 物种，获取资源需要高度灵活的、对环境敏感的社会行为系统 要求。事实上，僵化的社会行为可能是高度不适应的，特别是在发育阶段。 当社会需求不断变化时的过渡。然而，支持灵活社会的神经基础 发育过程中的行为一直没有得到充分的研究。为该提案收集的文献和试点数据 这让我提出了杏仁基底外侧核(BLA)及其多巴胺能(DA)的中心假说。 控制是社会行为回路的后期发展成分，它们的招募许可行为 灵活地将系统内部偏向社交的方式转变为更受限制的方式 随着婴儿获得独立，走进复杂的社会，L的世界。具体地说，这个大脑的目标是 K99-R00奖是应用先进的光学和电生理技术在幼鼠身上直接测试 这一假设有三个具体目的。目标1将在指导阶段(K99)执行，目的是 确定社交方法在发展过程中何时受到限制，以及BLA如何控制这一点。目标 2，在指导阶段(K99)期间启动，并在独立阶段(R00)期间完成，以确定 VTA DA释放到BLA中在使用汇聚性方法操纵的社交途径抑制中的作用 并测量血乳酸中的多巴胺水平。目标3，在独立阶段(R00)执行，将检查 长程VTA-BLA同步性与光遗传操纵DA的社会趋近性的关系 完成社会行为任务的大鼠VTA内神经元，同时记录VTA内的峰-LFP同步性 还有《洛杉矶公约》。对社交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。通过将先进的功能技术整合到研究中 对于复杂的婴儿行为，这项拟议的工作将在技术和概念上推动该领域的发展。

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.