Microcircuits underlying murine parental behavior

小鼠父母行为背后的微电路

基本信息

批准号：
8961097
负责人：
Catherine Dulac
金额：
$ 35.07万
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 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8961097
关键词：
Affect Aggressive behavior Agonistic Behavior Animals Area Automobile Driving Behavior Behavior Control Brain Caring Cells Characteristics Child Rearing Data Development Diagnosis Diagnostic Discipline of Nursing Disease Dissection Environmental Risk Factor Estradiol Exhibits Fathers Female Galanin Gene Expression Profiling Genetic Genetic Techniques Goals Grooming Health High Prevalence Hormonal Hormone Receptor Hormones Hypothalamic structure Impairment Infant Intrinsic factor Laboratory mice Major Depressive Disorder Mammals Maps Medial Mental disorders Molecular Molecular Genetics Mothers Motor Mouse Strains Mus Neural Pathways Neurons Neuropeptides Output Oxytocin Parents Partner in relationship Personal Satisfaction Physiological Population Postpartum Depression Posture Preoptic Areas Process Progesterone Prolactin Publishing Regulation Role Schizophrenia Social Behavior Social Interaction Specificity Stereotyping Stress Techniques Testing Therapeutic Work affiliative behavior autism spectrum disorder behavioral response burden of illness experience genetic approach genetic technology insight male neglect neural circuit neuronal circuitry novel novel therapeutic intervention offspring public health relevance pup relating to nervous system research study severe mental illness social therapeutic development tool urocortin

项目摘要

DESCRIPTION (provided by applicant): 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 propose to take advantage of newly developed molecular and genetic tools to uncover and characterize the specific neural populations and circuits involved in parental care, a social behavior essential for the survival and well-being of the offspring. Male and female mice show either affiliative or agonistic behavior toward infants depending on prior social experience. In recently published work, we uncovered a specific subpopulation of hypothalamic neurons that are essential for the control of male and female parenting behavior. This finding provides us with a unique entry point to genetically dissect behavior circuits underlying parental care and their modulation by intrinsic and environmental factors. Using a combination of genetic and functional tools, we aim to characterize the circuit involved in parental behavior (Aim I) and uncover neuronal subpopulations driving agonistic behavior toward pups (Aim II). We will determine the functional role of these genetically defined neural populations and associated projections in parenting or agonistic behavior toward pups using cutting-edge molecular techniques by tracing inputs and outputs to genetically defined neuronal populations and manipulating their activity. In Aim III, we will perform an unbiased gene expression analysis to discover factors influencing the differential activity of the neurons and circuits associated with affiliative or agonistic behavior in males and females, and in different physiological circumstances.

描述（由申请人提供）：许多具有相当大疾病负担的严重精神障碍，如自闭症谱系障碍、精神分裂症和重度抑郁症，其特点是严重的社会障碍，目前，人们对这些社会缺陷的根源知之甚少。缺乏诊断和治疗选择。先进的分子和遗传学技术使得发现参与社会行为的特定神经回路成为可能，从而促进针对社会缺陷疾病的诊断和新治疗方法的开发。新开发的分子和遗传工具来揭示和表征参与父母照顾的特定神经群体和回路，这是一种对父母照顾至关重要的社会行为在最近发表的研究中，雄性和雌性小鼠对婴儿表现出亲和或攻击行为，这对后代的生存和福祉至关重要。这一发现为我们提供了一个独特的切入点，可以从基因角度剖析父母关爱及其内在调节的行为回路。结合遗传和功能工具，我们的目标是描述与亲代行为有关的回路（目标 I），并揭示驱动幼崽攻击行为的神经元亚群（目标 II）。在目标 III 中，我们使用尖端分子技术，通过追踪基因定义的神经群体的输入和输出并操纵它们的活动，定义了神经群体以及对幼崽的养育或竞争行为的相关预测。将进行公正的基因表达分析，以发现影响男性和女性中与亲和或对抗行为相关的神经元和回路差异活动的因素女性，在不同的生理情况下。