Origin and timing of development of late-maturing neurons in the amygdala

杏仁核晚熟神经元发育的起源和时间

• 批准号: 10262956
• 负责人: JOSHUA G CORBIN
• 金额: $ 20.91万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10262956
• 关键词: ARHGEF5 gene; Adolescence; Adolescent; Adult; Age; Amygdaloid structure; Biophysics; Brain; Brain region; Bromodeoxyuridine; Cell Nucleus; Cells; Childhood; Communication; Data; Development; Dorsal; Electrophysiology (science); Embryo; Embryonic Development; Emotional; Female; Future; Genetic; Goals; Human; Interneurons; Lateral; Limbic System; Link; Mental disorders; Modeling; Molecular; Molecular Profiling; Morphology; Mus; Nature; Neurons; Neurosciences; Phenotype; Play; Population; Positioning Attribute; Primates; Process; Property; Role; Series; Social Behavior; Synapses; Systems Development; Time; Work; autism spectrum disorder; biocytin; cohort; critical period; developmental disease; emotional behavior; excitatory neuron; learned behavior; male; molecular marker; neurogenetics; novel; patch clamp; postnatal; postnatal development; prepuberty; progenitor; relating to nervous system; residence; social; tool

Project Summary The amygdala is a major processing center for emotional and social behaviors, aspects of which are altered in developmental disorders such as Autism Spectrum Disorders (ASD). In humans, the paralaminar nucleus of the amygdala (PL), located adjacent to basolateral amygdala amygdala (BLA), contains a large population of immature neurons that persist into post-natal stages, well past the maturational time course of the overwhelming majority of neurons in the brain. Our recent studies have revealed that human PL neurons mature prominently during childhood and adolescence (Sorrells et al., Nature Communications, 2019). This raises the intriguing possibility that these neurons are essential for social/emotional changes that occur during critical periods of postnatal development. Our preliminary data reveal that this population is also present in mice. This opens up an exciting opportunity to use the mouse to model this interesting neuronal population. The goals of this exploratory R21 application are to: 1) characterize the post-natal morphological, molecular and electrophysiological maturational profiles of mouse PL neurons during the pre-pubertal critical period temporally coinciding with emergence of emotional processing in humans and 2) determine the developmental timing and origin of mouse PL neurons. As embryonic origin and identity are intimately tied to adult neuronal function, these studies are also a important first step to ultimately dissecting neural connectivity, function and role that these specialized cells play in neuro-typical and -atypical social-emotional development.

项目摘要 杏仁核是情绪和社会行为的主要处理中心， 在自闭症谱系障碍（ASD）等发育障碍中发生改变。在人类中， 杏仁核内侧核（PL），位于基底外侧杏仁核附近 杏仁核（BLA）包含大量未成熟的神经元，这些神经元持续到出生后 阶段，远远超过了绝大多数神经元的成熟时间过程。 个脑袋我们最近的研究表明，人类PL神经元在 童年和青春期（Sorrells等人，Nature Communications，2019）。这就提出了一个 有趣的可能性是，这些神经元对发生在大脑中的社会/情感变化至关重要， 在产后发育的关键时期。我们的初步数据显示， 种群也存在于小鼠中。这为我们提供了一个激动人心的机会， 模拟这个有趣的神经元群体。此探索性R21应用程序的目标是： 1)表征出生后的形态，分子和电生理 小鼠PL神经元在青春期前关键期的成熟特征 时间上与人类情感处理的出现相一致，2） 确定小鼠PL神经元的发育时间和起源。作为胚胎起源 和身份与成人神经元功能密切相关，这些研究也是重要的第一次。 最终解剖神经连接，功能和作用，这些专门的细胞 在神经典型和非典型社会情感发展中发挥作用。