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: 10457839
• 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/10457839
• 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.

项目概要/摘要 社会功能受损是许多神经精神疾病的一个突出的、使人衰弱的症状，例如 如自闭症谱系障碍、精神分裂症和重度抑郁症。目前的神经基础 人们对这些社会缺陷知之甚少，并且仍然缺乏有效的治疗方法。说明 对社会行为的神经回路机制的研究将提高我们对疾病机制的理解 神经精神疾病的研究，促进有效治疗方法的开发。育儿行为已成为普遍现象 以及进化上古老的社会行为，对后代的生存和福祉产生严重影响 从无脊椎动物到人类，动物种类繁多，且具有显着差异 不同性别和生殖状态之间。尽管养育行为被认为是由 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然未定义。 此外，调节不同性别养育行为差异表现的神经机制 和生理状态知之甚少。解开这些问题将为我们提供重要的见解 养育行为背后的神经回路机制及其调节的基本原则 性二态行为。这些见解将提高我们对人类社会调节的理解 健康和疾病方面的行为。最近，我们发现了 GABAergic 的新功能作用 小鼠内侧杏仁核（MeA）中的神经元控制雌性养育行为和杀婴行为 男性的养育行为。我们还全面鉴定了分子异质 GABAergic 男性和女性 MeA 中的亚群。这些发现为深入研究提供了独特的机会 解剖新发现的大脑区域的功能组织，以严格控制养育和 杀婴行为。结合使用尖端的功能操作和成像技术，我们 旨在开发一种新的机制模型来解释不同 GABA 能亚群的差异激活 MeA 中规定了针对幼犬的相反行为。我们将解决一系列重要的核心问题 该模型：（1）养育和杀婴行为是由不同还是相同的 MeA GABAergic 控制的 亚群体（目标 1）？ （2）介导MeA GABA能神经元的下游神经回路有哪些？ 养育和杀婴行为（目标 2）？ (3) 神经元如何编码养育和杀婴行为 MeA GABA 能亚群的活动模式和传出预测（目标 3）？为了回答这些问题， 我们将对基因和投影定义的 MeA GABAergic 进行精确的功能操作 亚群及其轴突投影，并检查 MeA GABAergic 的神经活动动力学 在本地幼崽引导的行为期间，自由行为的动物的亚群及其预测。一起， 对这个模型的研究将为控制亲和和对抗的神经回路提供关键的、新颖的见解 对幼崽的行为以及控制性别二态性社会行为的一般原则。