Microcircuits underlying murine parental behavior

小鼠父母行为背后的微电路

基本信息

批准号：
10227959
负责人：
Catherine Dulac
金额：
$ 35.61万
依托单位：
HARVARD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-14 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10227959
关键词：
Adult Affect Aggressive behavior Agonistic Behavior Animals Architecture Area Atlases Behavior Behavioral Biophysics Calcium Caring Cell Nucleus Cells Child Rearing Development Diagnosis Diagnostic Disease Dissection Electrophysiology (science)Endocrine Fathers Female Functional disorder Funding Galanin Gene Expression Genetic Techniques Genetic Transcription Goals Grant Head Hormonal Hormone Receptor Human Hypothalamic structure Image Impairment In Situ Infant Infant Care Infanticide Lead Major Depressive Disorder Medial Mediating Mental Depression Molecular Molecular Genetics Monitor Mothers Motivation Motor Mus Neural Pathways Neuromodulator Receptors Neurons Partner in relationship Personal Satisfaction Pharmacology Physiological Population Preoptic Areas Regulation Resolution Role Schizophrenia Slice Social Behavior Social Interaction Specificity Stereotyping Synapses System Therapeutic Transcriptional Regulation Translating Variant Viral Work affiliative behavior autism spectrum disorder base biophysical properties biophysical techniques burden of illness caregiving cell type experience genetic technology imaging approach in vivo innovation male microendoscope microendoscopy neglect neural circuit neurobiological mechanism neuromechanism neurophysiology neuroregulation novel novel therapeutic intervention offspring pup relating to nervous system severe mental illness sex social social deficits therapeutic development tool urocortin

项目摘要

Project Summary/Abstract Many severe mental disorders with considerable disease burden such Autism Spectrum Disorders, Schizophrenia, and Major Depressive Disorder are characterized by profound social impairments. At present, there is little understanding of the origin of these social deficits, and efficient diagnosis and therapeutic options are lacking. Advanced molecular and genetic techniques make the discovery of specific neural circuits involved in social behavior possible, facilitating the development of diagnostics and novel therapeutic approaches specific to disorders with social deficits. We have taken advantage of newly developed molecular, genetic and systems- levels tools to uncover how specific neural populations and circuits involved in parental care, a social behavior essential for the survival and well-being of the offspring are regulated according to the animal sex and physiological status. Male and female mice show either affiliative or agonistic behavior toward infants depending on prior social experience. In recent work, we uncovered distinct subpopulations of hypothalamic neurons that are involved in the positive and negative regulation of male and female parenting behavior. The identification of these cell types with high granularity provides us with unique entry point to further dissect how changes in the molecular, biophysical and activity dynamics of distinct neuronal populations regulates parental care. We propose here to exploit the precise cell type identification of neuronal populations involved in the control of opposing infant-mediated behaviors and use high resolution molecular (Aim 1), neurophysiological (Aim 2) and systems-level (Aim 3) approaches to dissect the entire circuitry associated with infant-directed social interactions and to explore how these circuits are modulated by the animal’s sex and physiological state.

项目概要/摘要许多严重的精神障碍具有相当大的疾病负担，例如自闭症谱系障碍，精神分裂症和重度抑郁症的特点是严重的社会障碍。人们对这些社会缺陷的根源以及有效的诊断和治疗选择知之甚少缺乏先进的分子和遗传技术来发现所涉及的特定神经回路。可能的社会行为，促进诊断和新的具体治疗方法的发展我们利用了新开发的分子、遗传和系统来治疗具有社会缺陷的疾病。水平工具来揭示特定的神经群体和回路如何参与父母照顾（一种社会行为）对于后代的生存和福祉至关重要的物质根据动物性别和雄性和雌性小鼠对婴儿表现出亲和或攻击行为，具体取决于在最近的工作中，我们发现了下丘脑神经元的不同亚群。参与男性和女性养育行为的积极和消极调节。这些具有高颗粒度的细胞类型为我们提供了独特的切入点，以进一步剖析不同神经群体的分子、生物物理和活动动力学调节着父母的照顾。在此建议利用参与控制的神经群体的精确细胞类型识别反对婴儿介导的行为并使用高分辨率分子（目标 1）、神经生理学（目标 2）和系统级（目标 3）方法剖析与婴儿主导的社交互动相关的整个电路并探索这些回路如何受到动物性别和生理状态的调节。