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.

项目总结/摘要 终纹床核（BNST）是一个异质性脑区，在唤醒，焦虑， 和酒精成瘾它包含多个神经元亚群，其特征在于它们的 BNST内神经肽的表达和空间位置，其中一些是不同行为的基础 与酒精使用和戒断有关。两个这样的亚群表达促肾上腺皮质激素释放因子（CRF） 和胆囊收缩素（CCK）。从含有这些神经肽的BNST神经元到 在父母格兰特研究外侧下丘脑（LH），以确定其潜在的差异 饮酒行为和睡眠/觉醒状态的贡献。本补助金的父母补助金探讨了 由神经肽表达定义的BNST回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，BNST中神经肽的表达可能因性别而异。这 补充建立了父母补助金，以探索相同BNST神经元和投射的性别差异 在父母中学习。研究CRF-/CCK-表达量是否存在差异 BNST中的神经元及其向涉及压力、焦虑和觉醒的大脑区域的投射模式 将使研究人员对这个高度复杂的大脑区域有更细致的了解， 已知的过度饮酒和相关行为的性别差异。 父母资助还建议调查BNST中表达CRF的神经元的活动， 睡眠/醒来，而动物一直在饮酒，这将提供新的见解，这些作用 酒精相关睡眠障碍时的神经元。睡眠障碍是多种记录的影响之一， 酒精使用障碍据报道，酒精使用障碍患者也会出现焦虑， 在戒酒期间。本附录旨在进一步了解 通过记录CRF-/CCK-BNST活性，同时动物进行焦虑行为测试， 急性戒断长期饮酒。 该补充的候选人将领导拟议成为独立科学家的项目。 通过严格的实验技术培训和率先开发定制数据 分析管道收集的数据，她将获得宝贵的技能，将服务于她在未来的职业生涯， 科学在多位导师的指导下，她将致力于扩大她的合作者网络， 同行和导师她还将参加会议和研讨会系列，以实践她的科学传播 技能，并将有助于培训和指导更多的年轻科学家在实验室。在培训结束时 在此期间，她将为进入职业发展的下一个阶段做好充分的准备， 有竞争力的研究生课程，并提交申请，为未来的独立研究经费。