The Molecular Mechanisms Underlying Basolateral Amygdala Neuron Development

杏仁核是一个相互连接的核团，对行为、学习和记忆的情感和动机成分进行编码至关重要。杏仁核发育的扰动被认为有助于许多神经精神疾病，但无论是时间或精确的细胞基质受到这些扰动都没有很好的理解。因此，评估杏仁核的分子特性和发育程序对于理解神经精神疾病的病因是必不可少的。在这里，我建议破译的基因调控网络的基底外侧杏仁核复合体（BLA），一组主要由杏仁核的主要功能输入杏仁核的神经元细胞的发展所必需的。我们实验室的研究已经确定了在杏仁核能神经元发育中起关键作用的转录因子，类似于那些填充杏仁核的转录因子。在这个建议中，我将集中在一个转录因子，表征其在不同类型的BLA神经元的迁移和生存的作用，并确定其下游效应。为此，我将使用条件性敲除小鼠并进行单核RNA测序（snRNA-Seq），染色质免疫沉淀测序（ChIP-seq）和候选下游效应子的验证实验。细胞，分子和基因组技术在Sestan实验室建立良好，这方面的专业知识将使我能够阐明控制BLA神经元投射神经元规格和身份的分子过程，并有助于破译许多神经精神疾病的相关发育背景。

The amygdala is a formation of interconnected nuclei essential for encoding the emotional and motivational components of behavior, learning, and memory. Perturbations of amygdala development are thought to contribute to many neuropsychiatric disorders, but neither the timing of nor the precise cellular substrates subject to these perturbations are well understood. Consequently, assessing the molecular identities and developmental programs governing the amygdala is essential for understanding the etiology of neuropsychiatric disease. Here, I propose to decipher the gene regulatory networks necessary for the development of the basolateral amygdala complex (BLA), a group of nuclei comprised largely of glutamatergic cells that serve as the primary functional input to the amygdala. Studies from our laboratory have identified transcription factors that play critical roles in the development of glutamatergic neurons, similar to those that populate the amygdala. In this proposal I will focus on one transcription factor, characterizing its role in the migration and survival of different types of BLA glutamatergic neurons and identify its downstream effectors. To do so, I will use a conditional knockout mouse and conduct single nuclear RNA sequencing (snRNA-Seq), chromatin immunoprecipitation followed by sequencing (ChIP-seq), and validation experiments of candidate downstream effectors. Cellular, molecular, and genomic techniques are well established in the Sestan laboratory, and this expertise will allow me to both elucidate the molecular processes governing BLA glutamatergic projection neuron specification and identity and aid in deciphering the relevant developmental context underlying numerous neuropsychiatric disorders.