Characterizing the functional heterogeneity of the mouse paralaminar nucleus

表征小鼠板旁核的功能异质性

• 批准号: 10678525
• 负责人: David Saxon
• 金额: $ 3.5万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10678525
• 关键词: Action Potentials; Adolescence; Adolescent; Adult; Age; Amygdaloid structure; Animal Model; Area; Atlases; Behavior; Behavioral; Biological Models; Brain; Brain region; Categories; Cell Count; Cell Nucleus; Cells; Classification; Closure by clamp; Collaborations; Data; Databases; Development; Electrophysiology (science); Emotional; Fellowship; Goals; Growth; Heterogeneity; Hippocampus; Human; Individual; Injections; Knowledge; Label; Lateral; Light; Link; Maps; Measures; Membrane; Mental disorders; Microscopy; Molecular; Monkeys; Morphology; Mus; N-Methylaspartate; Neurons; Output; Pathology; Pattern; Phenotype; Physiological; Physiology; Play; Population; Post-Traumatic Stress Disorders; Pregnancy; Primates; Process; Property; Research; Role; Slice; Social Behavior; Source; Spike Potential; Subgroup; Synapses; Techniques; Testing; Training; Universities; Vertebral column; Viral; Virus; Work; autism spectrum disorder; base; biocytin; confocal imaging; density; electrical property; emotional behavior; entorhinal cortex; excitatory neuron; experimental study; gamma-Aminobutyric Acid; immunoreactivity; intercalation; mouse model; neuronal cell body; neuropsychiatric disorder; optogenetics; patch clamp; reconstruction; response; social

PROJECT SUMMARY/ABSTRACT The development of the amygdala includes an increase in size and cell number during adolescence, which is thought to confer maturation of emotional and social behaviors before adulthood. Perturbations in this process are associated with neuropsychiatric disorders and behavioral pathology; yet the cellular components of adolescent amygdala development are unknown. In humans, the paralaminar nucleus of the amygdala (PL) contains a large population of immature excitatory neurons that delay their maturation until adolescence. The PL may be a major contributor to adolescent amygdala development, but the physiology and connectivity of the region is yet to be investigated. Our recent work has shown the existence of an orthologous population in the mouse amygdala, opening a tractable model system to study the PL in detail. My initial electrophysiology experiments indicate putative physiological subgroups within the adult mouse PL. Based on past primate studies and the Allen Mouse Brain Connectivity atlas, inputs to and outputs from the adult PL may also show diversity. The goal of this proposal is to define the functional identity of the adult PL by classifying intrinsic electrical and morphological neuronal subtypes, dissecting their synaptic input patterns, and mapping their outputs. The training proposed in the advanced techniques of viral tracing, light sheet microscopy, whole-cell patch clamp, optogenetics, and morphological reconstruction will facilitate the exploration into the functional phenotypes of mouse PL neurons. These proposed studies are crucial to understanding the role of the PL in amygdala function and behavior, as well possible involvement in neuropsychiatric disorders.

项目总结/摘要 杏仁核的发育包括青春期大小和细胞数量的增加， 被认为在成年之前赋予情感和社会行为的成熟。这个过程中的扰动 与神经精神疾病和行为病理学有关;然而， 青少年杏仁核的发育是未知的。在人类中，杏仁核（PL） 含有大量未成熟的兴奋性神经元，这些神经元的成熟延迟到青春期。的PL 可能是青少年杏仁核发育的主要贡献者，但杏仁核的生理和连接性可能是一个重要因素。 该地区还有待调查。我们最近的工作表明，在一个正常的人口存在， 小鼠杏仁核，建立一个易于操作的模型系统，以详细研究PL。我最初的电生理检查 实验表明成年小鼠PL内的假定生理亚群。基于过去的灵长类动物研究 和艾伦小鼠脑连接性图谱，成人PL的输入和输出也可能显示多样性。 本提案的目标是通过将内在电和神经电分类来定义成人PL的功能特性， 形态神经元亚型，解剖它们的突触输入模式，并映射它们的输出。的 提出了病毒追踪、光片显微镜、全细胞膜片钳等先进技术的培训， 光遗传学和形态重建将有助于探索功能表型， 小鼠PL神经元。这些研究对于理解杏仁核功能中PL的作用至关重要 和行为，以及可能涉及神经精神疾病。