Encoding social arousal within prepronociceptin circuits in the extended amygdala

在扩展杏仁核的前诺西肽环路中编码社会唤起

• 批准号: 10736663
• 负责人: Jose Rodriguez-Romaguera
• 金额: $ 67.85万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-08 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10736663
• 关键词: Address; Amygdaloid structure; Anatomy; Arousal; Behavior; Behavior Disorders; Behavioral; Behavioral Assay; Biological; Brain; Brain region; Calcium; Cells; Characteristics; Complex; Disease; Exhibits; Exposure to; Fluorescent in Situ Hybridization; Food; Frequencies; Future; Generations; Genes; Genetic; Head; Heart; Human; Image; In Situ Hybridization; Individual; Intervention; Knowledge; Maps; Medial; Mediating; Motivation; Mus; Neurons; Odors; Partner in relationship; Pathway interactions; Patients; Personal Satisfaction; Physiological; Physiological Processes; Population; Preoptic Areas; Process; Pupil; Rabies; Research; Respiration; Role; Series; Sex Differences; Social Anxiety Disorder; Social Behavior; Social Interaction; Stimulus; Structure of terminal stria nuclei of preoptic region; Techniques; Technology; Testing; Therapeutic; Viral; avoidance behavior; behavior influence; behavioral response; experimental study; in vivo; motivated behavior; neural circuit; neural correlate; neuroimaging; neuropsychiatric disorder; neurotransmission; optogenetics; prepronociceptin; prevent; respiratory; response; segregation; sex; sexual dimorphism; social; social influence; success; tool; two-photon

TITLE Encoding social arousal within prepronociceptin circuits in the extended amygdala PROJECT SUMMARY/ABSTRACT As a social species, humans thrive on the ability to form social connections for individual well-being, survival, and societal success. Physiological arousal responses regulate this process by encoding information from social stimuli that guides subsequent behavioral actions. Dysregulation of the neural circuitry responsible for encoding arousal responses is thought to contribute to disturbed motivated behavior, a characteristic in many neuropsychiatric disorders. We can track the rapid changes in arousal responses by recording certain physiological metrics such as pupil size, frequency of heartbeats, and respiratory cycles, however, little is known about the neural circuits that regulate these rapid arousal responses and how they influence ongoing social behavior. We recently found that neurons that express the prepronociceptin gene in the BNST (BNSTPnoc neurons) encode the arousal responses that occur rapidly upon exposure to motivationally salient stimuli, such as predator and food odors. Interestingly, BNSTPnoc neurons project predominantly to the medial amygdala (MeA) and the medial preoptic area (mPOA), which are brain regions that regulate aspects of social motivation. Here, we will study how BNSTPnoc neurons that project to either MeA or mPOA regulate social arousal responses and modulate social behaviors. Our global hypothesis is that unique populations of BNSTPnoc neurons will selectively encode arousal responses to social stimuli in a stimulus-dependent manner and independent of encoding behavior. To accomplish this, we will precisely map afferent and efferent circuit connections of BNSTPnoc neurons (Aim 1), test the hypothesis that BNSTPnoc neurons encode social arousal responses (Aim 2), and test the hypothesis that neurons that encode arousal responses influence social behaviors (Aim 3). Identifying the function and natural dynamics of BNSTPnoc neurons is important because we currently do not understand the role of arousal in the generation of behavior and behavioral disorders, nor do we understand the circuitry underlying the contributions of arousal on social behavior. This gap in knowledge prevents us from developing therapeutic strategies that target this potentially critical biological substrate to treat disorders defined by maladaptive social behaviors.

标题 在延伸杏仁核的前原感受肽回路中编码社会唤醒 项目摘要/摘要 作为一个社会性物种，人类的繁荣依赖于为个人福祉、生存、 社会的成功。生理唤醒反应通过编码来自社交网络的信息来调节这一过程。 引导后续行为动作的刺激。负责编码的神经回路失调 唤醒反应被认为有助于扰乱动机行为，这是许多人的一个特征。 神经精神障碍我们可以通过记录某些 然而，诸如瞳孔大小、心跳频率和呼吸周期等生理指标知之甚少 关于调节这些快速唤醒反应的神经回路，以及它们如何影响正在进行的社会活动， 行为我们最近发现，在BNST中表达prepronociceptin基因的神经元（BNSTPnoc 神经元）编码在暴露于动机上显著的刺激时迅速发生的唤醒反应， 捕食者和食物的气味有趣的是，BNSTPnoc神经元主要投射到内侧杏仁核（MeA） 和内侧视前区（mPOA），这是调节社会动机的大脑区域。在这里， 我们将研究投射到MeA或mPOA的BNSTPnoc神经元如何调节社会唤醒反应， 调节社会行为。我们的总体假设是，BNSTPnoc神经元的独特群体将选择性地 以刺激依赖的方式和独立于编码的方式编码对社会刺激的唤醒反应 行为为了实现这一点，我们将精确地映射BNSTPnoc神经元的传入和传出回路连接。 (Aim 1），检验BNSTPnoc神经元编码社会唤醒反应的假设（目的2），并检验BNSTPnoc神经元编码社会唤醒反应的假设（目的2）。 假设编码唤醒反应的神经元影响社会行为（目标3）。识别 BNSTPnoc神经元的功能和自然动力学是重要的，因为我们目前还不了解BNSTPnoc神经元的作用。 在行为和行为障碍的产生中，我们也不了解潜在的电路， 性唤起对社会行为的影响这种知识上的差距阻碍了我们开发治疗性药物。 针对这种潜在的关键生物基质的策略，以治疗由适应不良的社会 行为。