Functional Dissection of Neural Circuitry Underlying Parenting Behavior

养育行为背后的神经回路的功能剖析

• 批准号: 10224738
• 负责人: Weizhe Hong
• 金额: $ 51.64万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-15 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10224738
• 关键词: Address; Affect; Agonistic Behavior; Amygdaloid structure; Animals; Area; Axon; Behavior; Brain; Brain region; Caring; Child Rearing; Data; Development; Disease; Dissection; Exhibits; Fathers; Female; Fiber; Health; Human; Imaging Techniques; Impairment; Infanticide; Invertebrates; Investigation; Major Depressive Disorder; Medial; Mediating; Mental disorders; Modeling; Molecular; Mothers; Mus; Nature; Neurons; Neuropeptide Gene; Output; Pattern; Personal Satisfaction; Photometry; Physiological; Public Health; Regulation; Reproduction; Research; Role; Schizophrenia; Series; Social Behavior; Social Functioning; Structure; Symptoms; Techniques; Testing; affiliative behavior; autism spectrum disorder; base; brain circuitry; disabling symptom; effective therapy; improved; insight; mRNA Differential Displays; male; neglect; neural circuit; neuromechanism; neuropsychiatric disorder; novel; offspring; optogenetics; pup; relating to nervous system; reproductive; sex; sexual dimorphism; single-cell RNA sequencing; social deficits; therapeutically effective

Project Summary/Abstract Impairments in social functioning is a prominent, debilitating symptom in many neuropsychiatric disorders, such as autism spectrum disorders, schizophrenia, and major depressive disorder. Currently the neural underpinnings of these social deficits are poorly understood, and effective therapeutic approaches are still lacking. Elucidation of the neural circuit mechanisms for social behaviors will improve our understanding of the disease mechanisms of neuropsychiatric disorders, facilitating the development of potent treatments. Parenting behavior is a prevalent and evolutionarily ancient social behavior that critically affects the survival and well-being of the offspring in a wide range of animal species from invertebrates to humans, and is characterized by remarkable differences between different sexes and reproductive states. Although parenting behavior is thought to be controlled by evolutionarily conserved neural circuits, the nature and functions of these circuits remain largely undefined. Furthermore, the neural mechanisms regulating the differential display of parenting behavior in different sexes and physiological states are poorly understood. Unraveling these questions will provide key insights into the neural circuit mechanisms underlying parenting behavior and the basic principles governing the regulation of sexually dimorphic behaviors. Such insights will improve our understanding on the regulation of human social behaviors in both health and disease. Recently, we have uncovered novel functional roles for GABAergic neurons in the mouse medial amygdala (MeA) in controlling parenting behavior in females and infanticidal and parenting behaviors in males. We have also comprehensively identified molecularly heterogeneous GABAergic subpopulations in both male and female MeA. These findings open up a unique opportunity for an in-depth dissection of the functional organization of a brain area newly identified to critically control parenting and infanticidal behaviors. Using a combination of cutting-edge functional manipulation and imaging techniques, we aim to develop a novel mechanistic model for how differential activations of distinct GABAergic subpopulations in the MeA regulate opposing pup-directed behaviors. We will address a series of important questions central to this model: (1) Are parenting and infanticidal behaviors controlled by different or the same MeA GABAergic subpopulations (Aim 1)? (2) What are the downstream neural circuits of MeA GABAergic neurons that mediate parenting and infanticidal behaviors (Aim 2)? (3) How are parenting and infanticidal behaviors encoded by neural activity patterns in MeA GABAergic subpopulations and efferent projections (Aim 3)? To answer these questions, we will perform precise, functional manipulations of genetically and projection-defined MeA GABAergic subpopulations and their axonal projections, and examine the neural activity dynamics of MeA GABAergic subpopulations and their projections in freely behaving animals during native pup-directed behaviors. Together, investigation of this model will yield key, novel insights into the neural circuitry governing affiliative and agonistic behaviors towards pups and the general principles underlying the control of sexually dimorphic social behaviors.

项目摘要/摘要 社会功能的障碍是许多神经精神疾病中的杰出症状，这是一种令人衰弱的症状， 作为自闭症谱系障碍，精神分裂症和重度抑郁症。目前神经基础 这些社会缺陷中的理解很少，并且仍然缺乏有效的治疗方法。阐明 社会行为的神经回路机制将提高我们对疾病机制的理解 神经精神疾病的疾病，促进有效治疗的发展。育儿行为很普遍 和进化上古老的社会行为，严重影响了后代的生存和福祉 从无脊椎动物到人类的广泛动物物种，其特征是显着差异 在不同的性别和生殖状态之间。尽管认为育儿行为是由 进化保守的神经回路，这些电路的性质和功能在很大程度上仍然不确定。 此外，调节不同性别育儿行为的差异表现的神经机制 生理状态知之甚少。解开这些问题将为您提供关键见解 育儿行为的基础神经电路机制和管理调节的基本原理 性二态行为。这种见解将提高我们对人类社会规范的理解 健康和疾病的行为。最近，我们发现了GABA能的新功能作用 小鼠内侧杏仁核（MEA）中的神经元在控制女性和杀婴育的育儿行为方面 男性的育儿行为。我们还全面鉴定出分子异质GABA能 男性和女性MEA的亚群。这些发现为深入的独特机会打开了 新近确定的大脑区域的功能组织的解剖，以控制育儿和 杀婴行为。使用尖端的功能操纵和成像技术的结合，我们 旨在开发一种新型的机械模型，用于如何不同的GABA能亚群的差异激活 在MEA中，调节相反的幼崽指导的行为。我们将解决一系列重要的问题 该模型：（1）是由不同或相同的MEA Gabaergic控制的育儿和杀婴行为 亚群（AIM 1）？ （2）介导的MEA GABA能神经元的下游神经回路是什么 育儿和杀婴行为（目标2）？ （3）如何通过神经编码育儿和杀婴行为 MEA GABA能亚群和传出预测中的活动模式（AIM 3）？要回答这些问题， 我们将对遗传和投影定义的MEA GABA能进行精确的功能操纵 亚群及其轴突投影，并检查MEA Gabaergic的神经活动动力学 在本地幼崽指导的行为中，亚群及其在自由行为的动物中进行的投影。一起， 对该模型的调查将产生关键的新见解，以对隶属和激动的神经回路 对幼崽的行为和对性二态社会行为控制的基础的一般原则。