Alcohol-related sleep disturbances and circuit dynamics of arousal neuropeptides

酒精相关的睡眠障碍和唤醒神经肽的回路动力学

• 批准号: 10617073
• 负责人: William J Giardino
• 金额: $ 9.03万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10617073
• 关键词: Acute; Affect; Alcohol consumption; Alcohol dependence; Alcohol withdrawal syndrome; Alcohols; Amygdaloid structure; Animals; Anxiety; Arousal; Behavior; Behavioral; Brain; Brain region; Cholecystokinin; Communication; Complex; Corticotropin-Releasing Hormone; Custom; Development; Funding; Future; Heavy Drinking; Hypothalamic structure; Investigation; Knowledge; Lateral; Location; Mental disorders; Mentors; Neurons; Neuropeptides; Parents; Patients; Pattern; Prevalence; Reporting; Research; Research Personnel; Role; Science; Scientist; Series; Sex Differences; Sleep; Sleep disturbances; Stress; Structure of terminal stria nuclei of preoptic region; System; Techniques; Training; Withdrawal; Work; alcohol effect; alcohol exposure; alcohol use disorder; anxiety-related behavior; behavior test; career; career development; data analysis pipeline; drinking behavior; insight; parent grant; peer coaching; programs; relating to nervous system; response; sex; skills; symposium

Project Summary/Abstract The bed nucleus of the stria terminalis (BNST) is a heterogeneous brain region with roles in arousal, anxiety, and alcohol addiction. It contains multiple subpopulations of neurons that can be characterized by their expression of neuropeptides and spatial locations within the BNST, some of which underlie distinct behaviors relevant to alcohol use and withdrawal. Two such subpopulations express corticotropin releasing factor (CRF) and cholecystokinin (CCK). Distinct projections from BNST neurons containing each of these neuropeptides to the lateral hypothalamus (LH) are investigated in the parent grant to determine their potential differential contributions to alcohol drinking behavior and sleep/wake states. The parent grant of this supplement explores how the BNST circuits defined by neuropeptide expression affect alcohol use and potential alcohol-related sleep disturbances. Past research suggests that the expression of neuropeptides in the BNST may differ by sex. This supplement builds off the parent grant to explore sex differences in the same BNST neurons and projections being studied in the parent. Studying whether there are differences in the amount of CRF-/CCK-expressing neurons in the BNST and in their projection patterns to brain regions involved in stress, anxiety, and arousal would allow researchers to have a more nuanced understanding of this highly complex brain region and the known sex differences in excessive alcohol consumption and related behaviors. The parent grant also proposes to investigate the activity of the CRF-expressing neurons in the BNST during sleep/wake while animals have been drinking alcohol, which will provide new insights into the role of these neurons during alcohol-related sleep disturbances. Sleep disturbance is one of multiple documented effects of alcohol use disorders. Anxiety has also been reported to develop in patients with alcohol use disorder, particularly during withdrawal from alcohol. This supplement aims to further our understanding of the mechanisms underlying this anxiety by recording CRF-/CCK-BNST activity while animals are undergoing anxiety behavior testing during acute withdrawal from long-term alcohol drinking. The candidate of this supplement will be leading the projects proposed to become an independent scientist. Through rigorous training on experimental techniques and spearheading the development of custom data analysis pipelines for the data collected, she will gain invaluable skills that will serve her in a future career in science. With the guidance of her multiple mentors, she will work on expanding her network of collaborators, peers, and mentors. She will also attend conferences and seminar series to practice her science communication skills and will contribute to the training and mentoring of more junior scientists in the lab. By the end of the training period, she will be very well prepared to both enter the next stages of her career development by applying to competitive graduate programs and submitting applications for future independent research funding.

项目摘要/摘要 Stria末端（BNST）的床核是一个异质的大脑区域，在唤醒，焦虑， 和酒精成瘾。它包含多个神经元的亚群，可以以其为特征 BNST内的神经肽和空间位置的表达，其中一些是基础的不同行为 与饮酒和戒酒有关。两个这样的亚群表达皮质激素释放因子（CRF） 和胆囊动蛋白（CCK）。来自包含这些神经肽的每一种的BNST神经元的不同投射 在父授予中研究了下丘脑（LH）的侧面下丘脑（LH），以确定其潜在差异 饮酒行为和睡眠/唤醒状态的贡献。该补充的父母赠款探索 神经肽表达定义的BNST电路如何影响酒精使用和潜在的酒精相关睡眠 干扰。过去的研究表明，神经肽在BNST中的表达可能因性别而异。这 补充剂建立父母的赠款，以探索同一BNST神经元和预测中的性别差异 在父母中学习。研究CRF-/CCK表达的量是否存在差异 BNST中的神经元及其投射模式在涉及压力，焦虑和唤醒的大脑区域 将使研究人员对这个高度复杂的大脑区域和 过度饮酒和相关行为的已知性别差异。 父母赠款还建议研究BNST中表达CRF神经元的活性 在动物喝酒时睡觉/唤醒，这将为这些角色提供新的见解 与酒精有关的睡眠障碍期间的神经元。睡眠障碍是多种记录的效果之一 酒精使用障碍。据报道，焦虑症患有饮酒障碍患者，尤其是 在戒酒期间。这种补充旨在进一步了解我们对基本机制的理解 通过记录CRF-/CCK-BN的这种焦虑，而动物正在进行焦虑行为测试 急性退出长期饮酒。 该补充剂的候选人将领导提议成为独立科学家的项目。 通过严格的实验技术培训并带头开发自定义数据 分析管道对收集的数据，她将获得宝贵的技能，这些技能将在未来的职业中为她服务 科学。在她的多个导师的指导下，她将努力扩大自己的合作者网络， 同龄人和导师。她还将参加会议和研讨会系列，以练习她的科学沟通 技能，将有助于实验室中更多初级科学家的培训和指导。在培训结束时 时期，她将通过申请将两者都付诸实践。 竞争性研究生计划并提交未来独立研究资金的申请。