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.

项目摘要 与生俱来的社会行为对生存至关重要，因此在动物物种中也是如此。在人类中，精神疾病 社交障碍包括自闭症谱系障碍和品行障碍。两个都是 这些情况可以在儿童早期发育期间观察到，并与杏仁核有关。 功能障碍。然而，仍然缺乏对大脑的回路和发育机制的了解。 社会行为的产生；我的目标是长期研究的主题。为了做到这一点，我把重点放在内侧 杏仁核(MEA)，因为它是一个与社会嗅觉线索的处理和 在老鼠身上产生社会运动动作。这个项目的目标是发现大脑的神经回路 对社会行为的感觉和运动的处理，特别是攻击性和发展 在雄性和雌性小鼠体内建立它们的机制。我会采取发展的方式来学习 通过利用我之前描述的Mea神经元亚群的攻击性，以 胚胎和出生后转录因子Foxp2的表达。MEA Foxp2+细胞在分子上和 在生理上与该地区其他发育定义的亚群截然不同。我向大家介绍一个中央 一种在社会信息的感觉加工过程中存在性别差异的假说 在MEA的出生后发育过程中产生，导致特定的下游功能回路。我要买下 整体方法，研究不同发展轨迹和不同性别的差异 环境条件。在目标1(K99)中，我将研究mea Foxp2+的细胞反应和功能 在攻击和其他社会行为中的雌性小鼠中的细胞 化学发生工具。在目标2(K99)中，我将建立MeA Foxp2+细胞在男性和 雌性小鼠发现攻击回路中特定性别的差异。在目标3(R00)中，我将研究 在青春期前和青春期后的不同时间点产生这些回路的发育机制。这就做 还要研究早年生活中的不良经历会如何改变该回路。在指导阶段， 获奖后，我将完成一项训练计划，以发展和加强成人和 幼鼠。通过集成一套不同的融合技术，包括多光纤测光、电路 在雄性和雌性小鼠的发育时间点绘制和基因编码的传感器图，这 该项目将极大地促进我们对建立 社会行为的性二态环路。