Development of the Basal Telencephalic Limbic System

更新提案的目标是揭示发展计划如何建立大脑 控制关键的社会和非社会行为的电路。我们之前的研究发现 杏仁核发育导致了发育转录因子中心模型，其中 我们假设边缘系统的发育、连接和先天行为特异性 子回路由胚胎表达的转录因子Dbx 1差异控制 Foxp2我们将在三个目标中测试这个模型，其中我们将：1）确定边缘系统 Dbx 1和Foxp 2衍生神经元的连接模式（具体目标1），2）细胞 由Dbx 1和Foxp 2调节的粘附分子（特异性目的2）和3）Dbx 1的功能 和Foxp 2在内侧杏仁核回路功能的形成/维持以及社交和非社交中的作用。 社会固有行为（具体目标3）。该假设的检验将使用 一个多样化和强大的组合，最先进的条件小鼠遗传学，神经元 电路绘图和基因分析方法沿着电生理学和先天行为 任务通过全面整合来自多个层面的分析数据，我们将发现 发育程序如何建立控制动机和先天 社会和非社会行为。此外，由于杏仁核功能障碍是一个主要特征， 许多流行的人类社会和情感障碍，包括吸毒成瘾行为， 自闭症谱系障碍，这项工作是至关重要的了解如何大脑电路 功能障碍导致药物滥用和成瘾行为。

The goal of the renewal proposal is to uncover how developmental programs establish brain circuitry controlling critical social and non-social behaviors. Our previous findings studying amygdala development have lead to a developmental transcription factor-centric model in which we hypothesize that development, connectivity and innate behavioral specificity of limbic subcircuits are differentially controlled by the embryonic expressed transcription factors, Dbx1 and Foxp2. We will test this model in three aims in which we will: 1) determine the limbic connectivity patterns of Dbx1- and Foxp2-derived neurons (Specific Aim 1), 2) the cell adhesion molecules regulated by Dbx1 and Foxp2 (Specific Aim 2) and 3) the function of Dbx1 and Foxp2 in the formation/maintenance of medial amygdala circuit function and social and non- social innate behaviors (Specific Aim 3). Testing of this hypothesis will be accomplished using a diverse and powerful combination of state of the art conditional mouse genetics, neuronal circuit mapping and gene profiling approaches along with electrophysiology and innate behavior tasks. By comprehensively integrating data from multiple levels of analyses, we will uncover how developmental programs establish brain circuitry that controls motivational and innate social and non-social behaviors. Moreover, as amygdala dysfunction is a prime feature of a host of prevalent human social and emotional disorders, including drug-addictive behaviors and autism spectrum disorders, this work is critical toward understanding how brain circuit dysfunction leads to substance abuse and addictive behaviors.