Emotional modulation of neural and behavioral responses to social cues by locus coeruleus

蓝斑对社会线索的神经和行为反应的情绪调节

• 批准号: 10378502
• 负责人: STEPHEN D SHEA
• 金额: $ 48万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-06-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10378502
• 关键词: Acute; Adult; Affect; Animals; Area; Arousal; Behavior; Behavioral; Brain; Brain Diseases; Cognition; Cues; Data; Dependence; Dopamine; Electrophysiology (science); Emotional; Event; Exhibits; Female; Fiber; Goals; Impairment; Learning; Major Depressive Disorder; Measures; Memory; Methods; Microdialysis; Midbrain structure; Motivation; Mus; Neurons; Norepinephrine; Odors; Output; Partner in relationship; Pathologic; Pattern; Phase; Photometry; Play; Positioning Attribute; Process; Regulation; Rewards; Role; Sensory; Shapes; Signal Transduction; Social Behavior; Social Interaction; Stimulus; Structure; Sucrose; Testing; Time; autism spectrum disorder; awake; behavioral response; drug of abuse; experience; locus ceruleus structure; motivated behavior; multimodality; novel; optogenetics; pup; relating to nervous system; repaired; response; reward processing; social; stem; temporal measurement; tool

PROJECT SUMMARY The goal of this proposal is to define the mechanisms by which noradrenaline (NA) from locus coeruleus (LC) attaches emotional significance to social cues and regulates socially-motivated behavior. Appropriate responses to rewarding stimuli are central to survival. Control of reward-driven behavior is most often associated with midbrain dopamine circuits. Yet, there is mounting evidence that the attractive potency (‘motivational salience’) of a given cue dynamically depends on a broader set of circuits signaling context and internal state. For example, responses to social rewards depend on their emotional significance. Adult female mice undergo dramatic changes in their response to mating and familial cues after their initial sexual and maternal experiences. These powerfully arousing experiences attach enduring emotional significance to social cues experienced during the encounter and increase their motivational salience. LC is a key structure for broadcasting arousal and emotional significance. Past studies strongly suggest that LC activity signals the emotional content of social cues, but due to the limited temporal resolution of the methods used in those studies, it is unclear whether LC affects motivated behavior by altering neural responses to social stimuli or by promoting specific behaviors. Here we propose to use high temporal resolution methods for recording neural activity, that have never before been performed in LC of animals freely engaging in social behavior. We will answer the question of whether LC spiking occurs predominantly in response to social sensory cues or in advance of behavioral choices. Our central hypothesis is that LC shapes social goal-directed behavior both by modulating the motivational salience of social cues and facilitating behavior responses. We aim to answer three outstanding questions regarding the contribution of LC activity to social behavior: (1) What is the timing of activity LC relative to social behaviors, and does it change with social experience? (2) How do tonic (sustained) activity and phasic (brief) activity contribute to behavior? and (3) How does LC input to downstream targets affect neural activity and behavioral responses. LC has long been indirectly implicated in the regulation of social behavior, but its specific online contribution to social interactions is not known. The significance of these studies lies in their potential to clarify this aspect of LC function and reconcile it with LC’s other roles in cognition, learning and control of arousal state.

项目摘要 本研究的目的是确定蓝斑去甲肾上腺素（NA） (LC)重视社会线索的情感意义，并调节社会动机的行为。 对奖励刺激的适当反应是生存的核心。控制奖励驱动的行为是最重要的 通常与中脑多巴胺回路有关。然而，越来越多的证据表明， 一个给定线索的动机显著性（“动机显著性”）动态地取决于一组更广泛的电路信号上下文， 内部状态。例如，对社会奖励的反应取决于它们的情感意义。成年女性 小鼠在初次交配后，对交配和家族线索的反应发生了巨大变化， 母亲的经验。这些强有力的唤起经验赋予社会持久的情感意义， 在遭遇过程中经历的线索，并增加他们的动机显着性。LC是一个关键结构， 传播着唤醒和情感意义过去的研究强烈表明，LC活动信号 社会线索的情感内容，但由于这些研究中使用的方法的时间分辨率有限， 目前尚不清楚LC是否通过改变对社会刺激的神经反应或通过促进 具体行为。在这里，我们建议使用高时间分辨率的方法来记录神经活动， 从未在LC动物自由参与社会行为中进行过。我们将回答 问题是LC尖峰是否主要发生在对社会感官线索的反应中，或者在 行为选择。我们的中心假设是，LC塑造社会目标导向的行为， 调节社会线索的动机显著性并促进行为反应。我们的目标是 回答了关于LC活动对社会行为的贡献的三个突出问题：（1）什么是 活动LC相对于社会行为的时间，它是否随社会经验而变化？(2)如何补药 （持续）活动和阶段性（短暂）活动对行为有影响吗？LC如何输入到下游 目标影响神经活动和行为反应。长期以来，LC一直间接参与监管 社会行为的影响，但其具体的在线贡献的社会互动是未知的。这些的意义 研究在于它们有可能澄清LC功能的这一方面，并将其与LC在认知中的其他作用相协调， 学习和控制唤醒状态。