Identity of late-maturing amygdala neurons in humans and mice

项目总结/文摘

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.