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 该提议的目的是定义核基因肾上腺素（Na）的机制 （LC）将情感意义附加到社会线索上，并调节社会动机的行为。 对奖励刺激的适当反应对于生存至关重要。控制奖励驱动的行为最多是 通常与中脑多巴胺电路有关。然而，有越来越多的证据表明有吸引力的效力 （给定的提示的“动机显着性”）动态地取决于一组更广泛的电路信号传导环境和 内部状态。例如，对社会奖励的回应取决于他们的情感意义。成年女性 老鼠在最初的性行为后对交配和家庭提示的反应发生了巨大变化 孕产妇的经验。这些有力的诱发经历将持久的情感意义带入社会 在相遇期间经历的提示并提高了他们的动机显着性。 LC是关键结构 广播唤醒和情感意义。过去的研究强烈表明LC活性信号 社交线索的情感内容，但由于这些研究中使用的方法的暂时分辨率有限， 目前尚不清楚LC是通过改变对社会刺激的神经反应还是通过促进来影响动机行为 特定行为。在这里，我们建议使用高临时分辨率方法记录神经活动， 从来没有在自由参与社会行为的动物的LC中进行过。我们将回答 LC峰值是否主要是针对社会感官提示还是在 行为选择。我们的核心假设是，LC构成了社会目标指导的行为 调节社会线索的动机显着性和支持行为反应。我们的目标 回答有关LC活动对社会行为的贡献的三个杰出问题：（1）什么是什么 活动LC相对于社会行为的时机，它会随社会经验而变化吗？ （2）滋补 （持续的）活动和阶段（简短）活动有助于行为？ （3）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一直间接与该调节有关 社会行为，但其对社交互动的特定在线贡献尚不清楚。这些的意义 研究在于它们的潜力阐明了LC功能的这一方面，并​​将其与LC在认知中的其他角色调和， 唤醒状态的学习和控制。