Developmental and circuit mechanisms for innate social behaviors in the medial amygdala

内侧杏仁核先天社会行为的发育和循环机制

• 批准号: 10442591
• 负责人: Julieta E Lischinsky
• 金额: $ 13.05万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442591
• 关键词: Address; Adolescent; Adult; Adverse event; Affect; Aggressive behavior; Amygdaloid structure; Animals; Award; Behavior; Brain; Brain region; Cells; Child; Child Development; Conduct Disorder; Cues; Development; Disease; Dissection; Embryo; Equilibrium; Event; FOXP2 gene; Female; Fiber; Functional disorder; Generations; Glutamates; Goals; Human; Instinct; Life; Life Experience; Medial; Mediating; Mental disorders; Mentors; Modeling; Molecular; Motor; Mus; Neurons; Output; Partner in relationship; Phase; Photometry; Physiological; Play; Population; Preoptic Areas; Preparation; Puberty; Regulation; Research Personnel; Research Proposals; Role; Sensory; Sex Differences; Social Behavior; Social Conditions; Social Interaction; Specificity; Sum; Synapses; Technical Expertise; Techniques; Testing; Therapeutic; Time; Training; autism spectrum disorder; density; experience; gamma-Aminobutyric Acid; holistic approach; improved; in vivo; male; maternal aggression; neural circuit; neuronal circuitry; novel; postnatal; postnatal development; ranpirnase; response; sensor; sex; sexual dimorphism; social; social deprivation; social influence; tool; transcription factor

Project Summary Innate social behaviors are crucial for survival, thus shared across animal species. In humans, psychiatric disorders with deficits in social interactions include autism spectrum disorders and conduct disorder. Both of these conditions can be observed during early child development and have been associated with amygdala dysfunction. However, there is still a lack of understanding of the circuitry and developmental mechanisms for the generation of social behaviors; topics I aim to study in the long-term. To do so, I focus on the medial amygdala (MeA) as it is a region that has been implicated in both the processing of social olfactory cues and the generation of social motor actions in mice. The goal of this project is to uncover the neuronal circuitry for the sensory and motor processing of social behaviors, specifically aggression, and the developmental mechanisms for their establishment in male and female mice. I will take a developmental approach to study aggression by taking advantage of my previously characterized MeA neuronal subpopulation, marked by the expression of the embryonic and postnatal transcription factor Foxp2. MeA Foxp2+ cells are molecularly and physiologically distinct from other developmentally-defined subpopulations in the region. I present a central hypothesis in which there are sexually dimorphic differences in the sensory processing of social information arising during postnatal development in the MeA, resulting in specific downstream functional circuits. I will take a holistic approach and study sex-specific differences at distinct developmental trajectories and under different environmental conditions. In Aim 1 (K99), I will investigate the cellular responses and functions of MeA Foxp2+ cells in female mice during aggression and other social behaviors through the use of fiber photometry and chemogenetic tools. In Aim 2 (K99), I will establish the MeA Foxp2+ cells downstream projections in male and female mice to uncover sex-specific differences in the circuits for aggression. In Aim 3 (R00), I will study the developmental mechanisms for the generation of these circuits at distinct time-points pre-and post-puberty. I will also investigate how the circuit may be modified by early life adverse experiences. In the mentored phase of the award, I will complete a training plan to develop and strengthen technical skills for circuit dissection in adult and juvenile mice. By integrating a diverse set of convergent techniques, including multi-fiber photometry, circuit mapping and genetically encoded sensors across developmental time-points in male and female mice, this project will greatly advance our understanding of the developmental mechanisms for the establishment of sexually dimorphic circuits for social behaviors.

项目概要 与生俱来的社会行为对于生存至关重要，因此在动物物种中是共有的。对于人类来说，精神科 社交互动缺陷的疾病包括自闭症谱系障碍和品行障碍。两者都 这些情况可以在儿童早期发育过程中观察到，并且与杏仁核有关 功能障碍。然而，人们对神经系统的电路和发育机制仍然缺乏了解。 社会行为的产生；我打算长期研究的主题。为此，我专注于内侧 杏仁核（MeA），因为它是一个与社会嗅觉线索的处理和处理有关的区域。 小鼠社会运动动作的产生。该项目的目标是揭示神经元回路 社会行为的感觉和运动处理，特别是攻击性，以及发展 它们在雄性和雌性小鼠中建立的机制。我将采取发展的方式来学习 通过利用我之前表征的 MeA 神经元亚群来进行攻击，其特征是 胚胎和出生后转录因子 Foxp2 的表达。 MeA Foxp2+ 细胞在分子上和 在生理上不同于该地区其他发育定义的亚群。我提出一个中央 社会信息的感觉处理存在性别二态性差异的假设 在 MeA 的出生后发育过程中产生，导致特定的下游功能回路。我会采取 采用整体方法，研究不同发展轨迹和不同条件下的性别差异 环境条件。在目标 1 (K99) 中，我将研究 MeA Foxp2+ 的细胞反应和功能 通过使用光纤光度法和 化学遗传学工具。在目标 2 (K99) 中，我将在男性和女性中建立 MeA Foxp2+ 细胞下游预测 雌性小鼠发现攻击性回路中性别特异性的差异。在目标 3 (R00) 中，我将学习 在青春期前后的不同时间点产生这些回路的发育机制。我会 还研究了早期生活中的不良经历如何改变回路。在辅导阶段 获奖后，我将完成一项培训计划，以发展和加强成人和青少年的电路解剖技术技能 幼年小鼠。通过集成多种会聚技术，包括多光纤光度测量、电路 在雄性和雌性小鼠的发育时间点上绘制和基因编码传感器，这 该项目将极大地增进我们对建立 社会行为的性别二态回路。