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.

项目总结/摘要 社会功能障碍是许多神经精神疾病中的一个突出的、使人衰弱的症状， 自闭症谱系障碍、精神分裂症和重度抑郁症。目前， 对这些社会缺陷的了解很少，仍然缺乏有效的治疗方法。阐发 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，促进有效治疗的发展。育儿行为是一种普遍的 和进化上古老的社会行为，严重影响后代的生存和福祉， 从无脊椎动物到人类的动物种类繁多，其特点是显著的差异 在不同的性别和生殖状态之间。虽然父母的行为被认为是由 尽管神经回路在进化上是保守的，但这些回路的性质和功能在很大程度上仍不确定。 此外，还探讨了不同性别父母教养行为差异的神经机制 和生理状态都知之甚少。解开这些问题将提供关键的见解， 父母教养行为的神经回路机制和调控的基本原则 两性异形行为这些见解将提高我们对人类社会调节的认识 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）神经元在控制雌性亲职行为和杀婴和 男性的养育行为。我们还全面鉴定了分子异质性GABA能 男性和女性MeA的亚群。这些发现为深入研究 解剖新发现的大脑区域的功能组织，以严格控制养育， 杀人行为。使用尖端的功能操作和成像技术相结合，我们 目的是开发一种新的机制模型，用于不同GABA能亚群的差异激活 调节着相反的小狗行为。我们将讨论一系列重要问题， 该模型：（1）育儿和杀婴行为是由不同还是相同的MeA GABA能控制的 亚群（目标1）？(2)MeA GABA能神经元的下游神经回路是什么， 父母养育和杀婴行为（目标2）？(3)父母养育子女和杀人行为是如何被神经系统编码的？ MeA GABA能亚群和传出投射的活动模式（目的3）？为了回答这些问题， 我们将对基因和投射定义的MeA GABA能进行精确的功能操作， 亚群及其轴突投射，并检查MeA GABA能神经活性动力学 亚群和他们的预测在自由行为的动物在本地小狗指导的行为。在一起， 对这一模型的研究将产生关键的、新的见解，了解支配亲和和竞争的神经回路。 对幼崽的行为和控制性二态社会行为的一般原则。