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.

项目概要/摘要 为了控制特定的行为反应，转录上不同的细胞类型被组装起来 进入动态大脑回路，将环境信息与内部状态整合起来，并生成 有目的的运动动作。虽然已经开发出独立测量活动的工具 单个神经元的动力学、连接性和转录特征，仍然具有挑战性 将这些不同的信息整合到一个连贯的行为模型中。为了应对这一挑战， 我们的目标是揭示导致复杂自然行为的感觉运动转变， 通过开发创新的分子、成像和系统级，男性和女性育儿 方法并通过整合从行为中的单个神经元获得的多模态信息 动物。在目标 1 中，我们将开发新工具来揭示活性和转录特性 涉及婴儿介导行为的神经元细胞类型。在目标 2 中，我们将探索分子、 功能和行为术语嗅觉和其他感觉方式如何成为养育的基础 男性和女性以及处女与交配状态下的行为。在目标 3 中，我们将研究如何 特定的下丘脑细胞类型使用反映行为结果的信息来处理 空间转录组学、功能成像、回路追踪和行为方法的结合。 在目标 4 中，我们将把基于细胞类型的神经元结构与跨关键的活动模式结合起来。 大脑区域来制定养育神经控制的预测模型。