The Molecular Mechanisms Underlying Basolateral Amygdala Neuron Development

杏仁核是一种相互连接的核，对编码行为、学习和记忆的情感和动机成分至关重要。杏仁核发育的扰动被认为是导致许多神经精神疾病的原因，但无论是受到这些扰动的时间还是精确的细胞底物都没有得到很好的理解。因此，评估控制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至关重要。在这里，我建议破译基础外侧杏仁核复合体（BLA）发育所必需的基因调控网络，这是一组主要由谷氨酸能细胞组成的细胞核，作为杏仁核的主要功能输入。我们实验室的研究已经确定了转录因子，这些转录因子在谷氨酸能神经元的发育中起着关键作用，类似于杏仁核中的那些。在本提案中，我将重点关注一种转录因子，表征其在不同类型BLA谷氨酸能神经元迁移和存活中的作用，并鉴定其下游效应物。为此，我将使用条件敲除小鼠，进行单核RNA测序（snRNA-Seq），染色质免疫沉淀后测序（ChIP-seq），以及候选下游效应物的验证实验。细胞，分子和基因组技术在Sestan实验室已经很好地建立起来，这些专业知识将使我能够阐明控制BLA谷氨酸能投射神经元规范和识别的分子过程，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.