Systems-Level and in Situ Transcriptomics Deconstruction of Neural Circuits Underlying Sensorimotor Transformation in an Innate Behavior

先天行为中感觉运动转化的神经回路的系统级和原位转录组学解构

• 批准号: 10709855
• 负责人: Catherine Dulac
• 金额: $ 141.98万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709855
• 关键词: Systems; Level; Situ; Transcriptomics; Deconstruction

Project Summary/Abstract In order to control specific behavioral responses, transcriptionally distinct cell types assembled into dynamic brain circuits integrate environmental information with internal states and generate purposeful motor actions. While tools have been developed to independently measure the activity dynamics, connectivity and transcriptional profiles of individual neurons, it remains challenging to integrate this diverse information into a coherent model of behavior. To address this challenge, we aim to uncover the sensorimotor transformations leading to a complex naturalistic behavior, male and female parenting, by developing innovative molecular, imaging and systems-level approaches and by integrating multimodal information obtained from single neurons in behaving animals. In aim 1, we will develop new tools to uncover the activity and the transcriptional identity of neuronal cell types involved in infant-mediated behavior. In aim 2, we will explore in molecular, functional, and behavioral terms how olfactory and other sensory modalities underlie parenting behavior in males and females and in virgin versus mated states. In aim 3, we will investigate how specific hypothalamic cell types process information reflecting behavioral outcomes using a combination of spatial transcriptomic, functional imaging, circuit tracing and behavioral methods. In aim 4, we will combine cell-type based neuronal architecture with activity patterns across key brain regions to formulate predictive models underlying the neural control of parenting.

项目摘要/摘要 为了控制特定的行为反应，转录上不同的细胞类型组装在一起 将环境信息与内部状态相结合，并生成 有目的的运动动作。虽然已经开发了工具来独立地测量活动 单个神经元的动力学、连通性和转录图谱，仍然具有挑战性 将这些不同的信息整合成一个连贯的行为模式。为了应对这一挑战， 我们的目标是揭示导致复杂自然主义行为的感觉运动转换， 通过发展创新的分子、成像和系统层面的男性和女性育儿 方法和通过整合从单个神经元获得的行为中的多模式信息 动物。在目标1中，我们将开发新的工具来揭示活动和转录身份 涉及婴儿中介行为的神经细胞类型。在目标2中，我们将从分子方面进行探索， 功能和行为术语嗅觉和其他感官形式如何构成育儿的基础 在雄性和雌性以及处女和交配状态下的行为。在目标3中，我们将研究如何 特定的下丘脑细胞类型使用 空间转录学、功能成像、电路追踪和行为方法的结合。 在目标4中，我们将结合基于细胞类型的神经元结构和跨键的活动模式 大脑区域来制定预测模型，这是父母养育的神经控制基础。