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.

概括 父母的忽视是常见的，并且对健康的人类发展非常有害。因此，更好 了解父母护理行为的生物学和护理后代的动机至关重要。 哺乳动物，几乎完全在一夫一妻制中观察到了稳健的父亲护理。发现神经 支持一夫一妻制的父亲护理的电路，我们建议开发和使用最先进的 分子和神经科学方面的工具研究了两个密切相关的peromyscus的父母行为 小鼠 - 一夫一妻制和一个混乱 - 父亲护理的极端差异。 我们已经为peromysscus小鼠建立了幼犬检索范例，我们使用多角度分析了该范式 摄影和机器学习姿势估计算法。此外，我们已经建立了病毒表达 和纤维植入的手术技术，使我们可以自由地形象和操纵神经回路 使用纤维光度法移动peromyscus小鼠。 首先，我们将量化幼犬的检索行为 - 啮齿动物的父母护理的重要组成部分 长期使用统计行为聚类和分类的第二个分辨率。然后，我们 将确定Peromyscus小鼠奖励系统中的差异神经元活性和多巴胺特征 在幼犬检索期间。最后，我们将在光遗传学上操纵多巴胺能奖励网络和 分析对规格和性别特异性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 和神经电路分析，结合了该属所表现出的丰富行为与现代神经回路 分析工具。这项工作将发现负责各种父母互动的电路原则 从忽视到健壮的父母护理，有了婴儿。