Microcircuits underlying murine parental behavior

小鼠父母行为背后的微电路

• 批准号: 9751346
• 负责人: Catherine Dulac
• 金额: $ 35.07万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 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/9751346
• 关键词: Affect; Aggressive behavior; Agonistic Behavior; Anatomy; Animals; Area; Automobile Driving; Behavior; Behavioral; 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; Motivation; 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; experimental study; genetic approach; genetic technology; insight; male; negative affect; neglect; neural circuit; neuronal circuitry; novel; novel therapeutic intervention; offspring; public health relevance; pup; relating to nervous system; severe mental illness; social; social deficits; therapeutic development; tool; urocortin

 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，例如自闭症谱系障碍、精神分裂症和重度抑郁症，其特征是严重的社会障碍。目前，人们对这些社会缺陷的根源知之甚少，也缺乏有效的诊断和治疗方案。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，从而促进了针对社交缺陷疾病的诊断和新型治疗方法的开发。我们建议利用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。 后代的生存和福祉。根据先前的社会经验，雄性和雌性小鼠对婴儿表现出亲和或对抗行为。在最近发表的工作中，我们发现了下丘脑神经元的一个特定亚群，它们对于控制男性和女性养育行为至关重要。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背后的行为回路及其内在的调节作用。 和环境因素。使用遗传和功能工具的组合，我们的目标是描述与父母行为有关的回路（目标 I），并揭示驱动幼崽竞争行为的神经元亚群（目标 II）。我们将使用尖端分子技术，通过追踪基因定义的神经元群体的输入和输出并操纵它们的活动，确定这些基因定义的神经群体的功能作用以及在养育或对幼崽的竞争行为中的相关预测。在目标 III 中，我们 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。