Development of the Basal Telencephalic Limbic System

描述(申请人提供)：本次续展申请侧重于杏仁核基底外侧复合体和内侧核的发育研究。总体而言，这些核团调节边缘系统功能的主要方面。我们之前的研究已经在发育中的端脑中发现了不同的祖细胞池，这些祖细胞池有助于这些杏仁核分区中出生后神经细胞的多样性。在这项工作的基础上，在这个项目中，我们将检验两个假设。首先，我们将检验这一假设，即杏仁核前体细胞池中胚胎转录因子表达的多样性是出生后杏仁核神经元亚型命运和轴突连接模式差异的基础。其次，我们将检验这样一个假设，即在这些祖细胞结构域中表达的关键转录因子对于来自这些群体的出生后杏仁核神经元的发育和/或连接是必需的。这些假说的检验将使用包括遗传命运图谱、电生理学、轴突追踪和条件性功能丧失在内的综合尖端方法来完成。 与公共健康相关：哺乳动物的杏仁核是大脑边缘系统的中心结构，大脑边缘系统是一个大脑回路，协调对刺激的适当行为反应，具有情绪和动机的突出。杏仁核功能障碍与许多大脑疾病有关，包括成瘾行为和发育障碍，如自闭症谱系障碍。这一建议旨在了解杏仁核发育的遗传和细胞基础，从而为人类杏仁核功能改变的疾病提供有价值的见解。

DESCRIPTION (provided by applicant): This renewal application is focused on the study of the development of the basolateral complex and medial nucleus of the amygdala. Collectively these nuclei regulate major aspects of limbic system function. Our previous studies have identified distinct progenitor pools in the developing telencephalon that contribute to postnatal neuronal cell diversity in these amygdala subdivisions. Based on this work, in this project we will test two hypotheses. First, we will test the hypothesis that embryonic transcriptional factor expression diversity within amygdala progenitor pools underlies differential postnatal amygdala neuronal subtype fate and patterns of axonal connectivity. Second, we will test the hypothesis that key transcription factors that are expressed in these progenitor domains are required for the development and/or connectivity of postnatal amygdala neurons that are derived from these populations. Testing of these hypotheses will be accomplished using a combination cutting edge approaches including genetic fate mapping, electrophysiology, axonal tracing and conditional loss of function. PUBLIC HEALTH RELEVANCE: The mammalian amygdala is a central structure of the brain's limbic system, a brain circuit that coordinates appropriate behavioral responses to stimuli with emotional and motivational salience. Amygdala dysfunction is associated with numerous brain disorders including addictive behavior and developmental disorders such as autism spectrum disorders. This proposal is directed toward understanding the genetic and cellular basis of amygdala development, and thus will provide valuable insight into human disorders in which amygdala function is altered.