Development of the Basal Telencephalic Limbic System

更新提案的目标是揭示发展项目如何建立大脑 控制关键社会和非社会行为的回路。我们之前的研究发现 杏仁核发育导致了以转录因子为中心的发育模式 我们假设边缘的发育、连通性和先天的行为特异性 亚电路受胚胎表达的转录因子Dbx1的差异控制 和Foxp2。我们将从三个方面测试这个模型：1)确定边缘 Dbx1和Foxp2来源神经元的连接模式(特定目标1)，2)细胞 Dbx1和Foxp2调节的黏附分子(特异靶向2)和3)Dbx1的功能 和Foxp2在杏仁核内侧环路的形成/维持中的作用及社会和非 社会先天行为(具体目标3)。对这一假设的检验将使用 一种多样化和强大的组合，条件小鼠遗传学，神经元 电路作图和基因图谱方法以及电生理学和先天行为 任务。通过综合整合来自多个层次的分析数据，我们将发现 发育程序如何建立控制动机和先天的大脑回路 社会行为和非社会行为。此外，由于杏仁核功能障碍是老年痴呆症的主要特征。 一系列流行的人类社会和情绪障碍，包括吸毒成瘾行为和 自闭症谱系障碍，这项工作对于了解大脑电路如何 功能障碍会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.