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Functional Dissection of Neural Circuitry Underlying Parenting Behavior

养育行为背后的神经回路的功能剖析

基本信息

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
项目类别：
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

项目摘要

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/文摘