Identity of late-maturing amygdala neurons in humans and mice

项目摘要/摘要 青春期是人类社会/情感发展的关键窗口。这一时期的特点是 杏仁核的生长，它的大小和神经元数量都增加了。我们最近描述了一种独特的 人杏仁核板旁核的神经发育形式。这个地区有一个人口 与其他神经元相比，发育时间延迟的未成熟神经元。这些神经元成熟 在青春期，他们会形成兴奋性神经元。在小鼠的初步研究中，一只容易驯服的 动物模型中，我们发现了一群未成熟的神经元，它们共享分子、解剖和 人类发育迟缓神经元的形态特征。此外，它们成熟的时间表 在两个物种中看起来相似。尽管它们在出生后仍然不成熟，但这些晚熟的 神经元是在胚胎神经发生过程中诞生的。这项提议的目的是为了揭示事态的发展， 晚熟杏仁核神经元从发生到功能的突触整合和分子多样性 利用人类和老鼠进行整合。综合使用最先进的方法，我们建议 通过以下方式实现这一目标：1)跟踪晚熟早熟幼虫的胚胎和出生后发育动态 小鼠的神经元(特定目标1)，2)识别晚成熟的杏仁核神经元何时以及如何发挥功能 整合到小鼠现有的杏仁核回路中(特定目标2)和3)发现和比较 小鼠和人的迟熟PL神经元分子多样性(特定目标3)。在这个跨物种的项目中 我们将讨论有关一种尚未探索的神经元形式的发育和成熟的主要问题 青春期发生在青春期关键阶段的发育。这项工作是未来必不可少的第一步 这些神经元在社会/情绪行为中的作用及其延迟控制机制的研究 发展及其对人类行为病理生理学的意义。

PROJECT SUMMARY/ABSTRACT Adolescence is a key window for social/emotional development in humans. This period is characterized by growth of the amygdala, which increases in both size and neuron number. We recently described a unique form of neurodevelopment in the human amygdala paralaminar nuclei (PL). This region contains a population of immature neurons that develop on a delayed timeline relative to other neurons. These neurons mature during adolescence when they will form excitatory neurons. In preliminary studies in the mouse, a tractable animal model, we found a population of immature neurons that share molecular, anatomical, and morphological features with late-developing neurons in humans. Additionally, the timeline of their maturation appears similar in both species. Although they remain immature during postnatal ages, these late-maturing neurons are born during embryonic neurogenesis. The goal of this proposal is to uncover the development, synaptic integration and molecular diversity of late-maturing amygdala neurons from genesis to functional integration using both humans and mice. Using a combination of state of the art approaches, we propose to accomplish this goal by: 1) Tracking the embryonic and postnatal developmental dynamics of late-maturing PL neurons in mice (Specific Aim 1), 2) identifying when and how late-maturing amygdala neurons functionally integrate into existing amygdala circuitry in mice (Specific Aim 2) and 3) uncovering and comparing late-maturing PL neuron molecular diversity in mice and humans (Specific Aim 3). In this cross-species project we will address major questions about the development and maturation of an unexplored form of neuron development that occurs during the critical stage of adolescence. This work is an essential first step for future studies of the role of these neurons in social/emotional behavior, mechanisms controlling their delayed development, and their significance to human behavioral pathophysiology.