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

基本信息

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
项目类别：
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

项目摘要

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.

标题在扩展杏仁核的前诺西肽环路中编码社会唤起项目概要/摘要作为一个社会物种，人类的繁荣依赖于为个人福祉、生存、和社会成功。生理唤醒反应通过编码来自社会的信息来调节这一过程指导后续行为行动的刺激。负责编码的神经回路失调唤醒反应被认为会导致动机行为紊乱，这是许多人的一个特征神经精神疾病。我们可以通过记录某些特定的行为来追踪唤醒反应的快速变化然而，人们对瞳孔大小、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持续的社交行为。我们最近发现在 BNST 中表达 prepronociceptin 基因的神经元（BNSTPnoc 神经元）编码在暴露于动机显着刺激时迅速发生的唤醒反应，例如如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），它们是调节社会动机方面的大脑区域。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，独特的 BNSTPnoc 神经元群体会选择性地以刺激依赖性方式编码对社会刺激的唤醒反应，并且独立于编码行为。为了实现这一目标，我们将精确绘制 BNSTPnoc 神经元的传入和传出电路连接（目标 1），检验 BNSTPnoc 神经元编码社交唤醒反应的假设（目标 2），并检验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很重要，因为我们目前还不了解其作用行为和行为障碍的产生中的唤醒，我们也不了解潜在的电路觉醒对社会行为的贡献。这种知识上的差距阻碍了我们开发治疗方法针对这种潜在的关键生物基质来治疗由适应不良的社会定义的疾病的策略行为。