Microcircuits underlying murine parental behavior

小鼠父母行为背后的微电路

• 批准号: 10674853
• 负责人: Catherine Dulac
• 金额: $ 35.61万
• 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 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10674853
• 关键词: Adult; Affect; Aggressive behavior; Agonistic Behavior; Animals; Architecture; Area; Atlases; Behavior; Behavioral; Biophysics; Calcium; Caring; Cell Nucleus; Cells; Child Rearing; Dedications; Development; Diagnosis; Diagnostic; Disease; Dissection; Electrophysiology (science); Endocrine; Fathers; Female; Functional disorder; Funding; Galanin; Gene Expression; Genetic; Genetic Techniques; Genetic Transcription; Goals; Grant; Head; Hormonal; Hormone Receptor; Human; Hypothalamic structure; Image; Impairment; In Situ; Infant; Infant Care; Infanticide; Major Depressive Disorder; Medial; Mediating; Mental Depression; Molecular; Monitor; Mothers; Motivation; Motor; Mus; Neural Pathways; Neuromodulator Receptors; Neurons; Partner in relationship; Personal Satisfaction; 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; biophysical properties; biophysical techniques; burden of illness; caregiving; cell type; experience; genetic approach; genetic technology; imaging approach; in vivo; innovation; male; microendoscope; microendoscopy; neglect; neural; neural circuit; neurobiological mechanism; neuromechanism; neurophysiology; neuroregulation; novel; novel therapeutic intervention; offspring; pharmacologic; pup; severe mental illness; sex; social; social deficits; therapeutic development; tool; urocortin

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.

项目总结/摘要 许多严重的精神障碍与相当大的疾病负担，如自闭症谱系障碍， 精神分裂症和重度抑郁症的特征是严重的社会障碍。目前， 对这些社会缺陷的起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使得发现特定的神经回路参与 在社会行为可能，促进诊断和新的治疗方法的发展，具体 社会缺陷的障碍。我们利用了新开发的分子遗传系统- 水平的工具，以揭示如何特定的神经群体和电路参与父母的照顾，社会行为， 对后代的生存和健康至关重要的是根据动物的性别进行调节， 生理状态雄性和雌性小鼠对婴儿表现出亲和或对抗行为， 之前的社会经验。在最近的工作中，我们发现了下丘脑神经元的不同亚群， 参与了男性和女性养育行为的积极和消极调节。的识别 这些高粒度的细胞类型为我们提供了独特的切入点，以进一步剖析细胞中的变化， 不同神经元群体的分子、生物物理和活动动力学调节父母的照顾。我们 在这里，我建议利用精确的细胞类型识别参与控制的神经元群体， 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 系统层次（目标3）的方法来剖析与婴儿导向的社会互动相关的整个回路 并探索这些回路是如何被动物的性别和生理状态所调节的。

项目成果

Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region.

下丘脑前区域的分子，空间和功能性单细胞分析。

• DOI: 10.1126/science.aau5324
• 发表时间: 2018-11-16
• 期刊: Science (New York, N.Y.)
• 作者: Moffitt JR;Bambah-Mukku D;Eichhorn SW;Vaughn E;Shekhar K;Perez JD;Rubinstein ND;Hao J;Regev A;Dulac C;Zhuang X
• 通讯作者: Zhuang X

Mapping of Brain Activity by Automated Volume Analysis of Immediate Early Genes.

• DOI: 10.1016/j.cell.2016.05.007
• 发表时间: 2016-06-16
• 期刊: Cell
• 影响因子: 64.5
• 作者: Renier N;Adams EL;Kirst C;Wu Z;Azevedo R;Kohl J;Autry AE;Kadiri L;Umadevi Venkataraju K;Zhou Y;Wang VX;Tang CY;Olsen O;Dulac C;Osten P;Tessier-Lavigne M
• 通讯作者: Tessier-Lavigne M

Functional circuit architecture underlying parental behaviour.

• DOI: 10.1038/s41586-018-0027-0
• 发表时间: 2018-04
• 期刊: Nature
• 影响因子: 64.8
• 作者: Kohl J;Babayan BM;Rubinstein ND;Autry AE;Marin-Rodriguez B;Kapoor V;Miyamishi K;Zweifel LS;Luo L;Uchida N;Dulac C
• 通讯作者: Dulac C

Urocortin-3 neurons in the mouse perifornical area promote infant-directed neglect and aggression.

小鼠穹窿周围区域的 Urocortin-3 神经元会促进婴儿的忽视和攻击行为。

• DOI: 10.7554/elife.64680
• 发表时间: 2021-08-23
• 期刊: eLife
• 影响因子: 7.7
• 作者: Autry AE;Wu Z;Kapoor V;Kohl J;Bambah-Mukku D;Rubinstein ND;Marin-Rodriguez B;Carta I;Sedwick V;Tang M;Dulac C
• 通讯作者: Dulac C

The neurobiology of parenting: A neural circuit perspective.

• DOI: 10.1002/bies.201600159
• 发表时间: 2017-01
• 期刊: BioEssays : news and reviews in molecular, cellular and developmental biology
• 作者: Kohl J;Autry AE;Dulac C
• 通讯作者: Dulac C