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

项目总结 这项提议的目的是确定蓝斑中去甲肾上腺素(NA)的机制。 (LC)重视社会暗示的情感意义，并规范社会动机行为。 对奖励刺激的适当反应是生存的核心。对奖励驱动的行为的控制是最重要的 通常与中脑多巴胺回路有关。然而，越来越多的证据表明，这种诱人的力量 给出的提示(动机显著程度)动态地取决于更广泛的电路信号发送上下文和 内部状态。例如，对社会奖励的反应取决于它们的情感重要性。成年女性 小鼠在初次有性行为后，对交配和家庭暗示的反应发生了戏剧性的变化 母性经历。这些强烈的唤醒经历赋予了社会持久的情感意义 在相遇过程中经历的暗示，并增加他们的动机突显。LC是一个关键的结构， 传播唤醒和情感的意义。过去的研究强烈表明，LC活动发出信号 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是通过改变对社会刺激的神经反应还是通过促进 特定的行为。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，即 以前从未在自由从事社会行为的动物的LC中表演过。我们将回答 关于LC尖峰是否主要发生在对社会感官提示的反应或先于 行为选择。我们的中心假设是LC通过以下两种方式塑造社会目标导向行为 调节社交线索的动机突显，促进行为反应。我们的目标是 回答关于LC活动对社会行为的贡献的三个突出问题：(1)什么是 LC活动的时间与社会行为的关系，以及它是否随社会经验而改变？(2)补药如何 (持续性)活动和阶段性(短暂)活动对行为有贡献吗？以及(3)LC如何输入到下游 目标会影响神经活动和行为反应。LC长期以来一直间接卷入这一监管规定 社交行为，但它在网上对社交互动的具体贡献尚不清楚。这些因素的意义 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， 觉醒状态的学习和控制。

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.