Identity of late-maturing amygdala neurons in humans and mice

项目总结/摘要 青春期是人类社会/情感发展的关键窗口。这个时期的特点是 杏仁核的生长，其大小和神经元数量都增加。我们最近描述了一种独特的 人类杏仁核的神经发育形式。这个地区的人口 相对于其他神经元而言，未成熟的神经元在延迟的时间轴上发育。这些神经元成熟后 在青春期形成兴奋性神经元。在小鼠的初步研究中， 在动物模型中，我们发现了一群未成熟的神经元，它们具有相同的分子，解剖学和生物学特征。 人类晚期发育神经元的形态特征。此外，他们成熟的时间轴 这两个物种看起来很相似。虽然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产生的。这项提案的目的是揭示发展， 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 使用人类和小鼠的整合。使用最先进方法的组合，我们建议 通过以下方式实现这一目标：1）跟踪晚熟PL的胚胎和出生后发育动态 神经元在小鼠（具体目标1），2）确定何时以及如何晚熟杏仁核神经元功能 整合到小鼠现有杏仁核回路中（具体目标2）和3）揭示和比较 小鼠和人类中的晚熟PL神经元分子多样性（具体目标3）。在这个跨物种的项目中 我们将讨论一种尚未探索的神经元形式的发育和成熟的主要问题 在青春期的关键阶段发生的发展。这项工作是未来重要的第一步。 研究这些神经元在社会/情感行为中的作用，控制其延迟的机制， 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.