Determining the role of reward circuits behind different paternal care behaviors and the motivation to care for offspring by comparing two animal models

通过比较两种动物模型来确定不同父亲照顾行为背后的奖励回路的作用以及照顾后代的动机

• 批准号: 10577852
• 负责人: Andrés Bendesky
• 金额: $ 20.56万
• 依托单位: COLUMBIA UNIV NEW YORK MORNINGSIDE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10577852
• 关键词: 3-Dimensional; Acceleration; Adult; Algorithms; Animal Behavior; Animal Model; Animals; Back; Base Sequence; Behavior; Behavioral; Biological Models; Biology; Caring; Cations; Child; Classification; Computer software; Data; Discipline of Nursing; Dopamine; Fathers; Female; Fiber; Globus Pallidus; Grooming; Human Development; Image; Impairment; Individual; Infant; Jaw; Machine Learning; Mammals; Medial; Mental Health; Modernization; Molecular; Mothers; Motivation; Mus; Nature; Neurons; Nucleus Accumbens; Operative Surgical Procedures; Output; Parents; Paternal Behavior; Pattern; Peromyscus; Photometry; Play; Population; Postpartum Period; Pregnancy; Publishing; Rattus; Resolution; Retrieval; Rewards; Rodent; Role; Signal Transduction; Social Interaction; System; Techniques; Variant; Ventral Tegmental Area; Video Recording; Viral; Work; calcium indicator; experimental study; implantation; kinematics; light gated; loss of function; mRNA Differential Displays; markov model; mind control; neglect; neural; neural circuit; neural stimulation; offspring; optogenetics; pup; redshift; reward circuitry; sensor; sex; species difference; time use; tool; willingness

Summary Parental neglect is common and highly detrimental to healthy human development. Therefore, a better understanding of the biology of parental care behavior and the motivation to care for offspring is critical. In mammals, robust paternal care is observed almost exclusively in monogamous species. To discover the neural circuitry supporting paternal care in monogamous species, we propose to develop and use state-of-the-art molecular and neuroscientific tools to study parental behavior in two closely related species of Peromyscus mice —one monogamous and one promiscuous— with extreme differences in paternal care. We have established a pup retrieval paradigm for Peromyscus mice that we analyze using multi-angle videography and machine-learning pose-estimation algorithms. Furthermore, we have set up viral expression and surgery techniques for fiber implantation such that we can image and manipulate neural circuits in freely moving Peromyscus mice using fiber photometry. First, we will quantify pup retrieval behavior —an essential component of parental care in rodents— with sub- second resolution over long periods of time using statistical behavioral clustering and classification. Then, we will identify differential neuronal activity and dopamine signatures in the reward system of Peromyscus mice during pup retrieval. Finally, we will optogenetically manipulate nodes of the dopaminergic reward network and analyze the effects on species- and sex-specific pup retrieval behavior. Our experimental and analytical approach will establish Peromyscus as a model system for detailed behavior and neural circuit analysis, combining the rich behavior displayed by this genus with modern neural circuit analysis tools. This work will discover circuit principles responsible for the vast range of parental interactions with infants, from neglect to robust parental care.

总结 父母的忽视很常见，对人类的健康发展非常有害。因此，更好的 了解父母照顾行为的生物学和照顾后代的动机至关重要。在 在哺乳动物中，几乎只在一夫一妻制的物种中观察到强大的父爱。去发现神经 支持一夫一妻制物种的父亲照顾电路，我们建议开发和使用最先进的 分子和神经科学工具来研究两种密切相关的Peromyscus物种的父母行为 老鼠-一个一夫一妻制和一个滥交-在父亲的照顾极端差异。 我们已经建立了一个小白鼠检索范式，我们分析了使用多角度 视频和机器学习姿态估计算法。此外，我们还建立了病毒表达 以及纤维植入的外科技术，这样我们就可以自由地成像和操纵神经回路， 移动Peromyscus小鼠，使用纤维光度法。 首先，我们将量化幼鼠的检索行为-啮齿动物父母照顾的重要组成部分-与子， 使用统计行为聚类和分类在长时间内实现第二分辨率。然后我们 将确定Peromyscus小鼠奖励系统中的差异神经元活动和多巴胺特征 在取回幼犬的过程中最后，我们将光遗传学操纵多巴胺能奖励网络的节点， 分析对特定物种和性别的幼崽检索行为的影响。 我们的实验和分析方法将建立Peromyscus作为详细行为的模型系统 和神经回路分析，将该属植物表现出的丰富行为与现代神经回路相结合 分析工具。这项工作将发现电路的原则负责的广泛的父母互动 与婴儿，从忽视到强大的父母照顾。