Cortical-noradrenaline signaling in alcohol behavioral engagement

酒精行为参与中的皮质-去甲肾上腺素信号传导

• 批准号: 10808515
• 负责人: Phillip A Starski
• 金额: $ 14.45万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10808515
• 关键词: Address; Advisory Committees; Alcohol abuse; Alcohol consumption; Alcohols; Anatomy; Animals; Anterior; Attention; Attenuated; Award; Awareness; Behavior; Behavior assessment; Behavioral; Behavioral Paradigm; Brain; Chronic; Clinical; Collaborations; Communities; Consumption; Data Set; Dedications; Disease; Electrophysiology (science); Ensure; Environment; Faculty; Foundations; Future; Genetic; Genetic Predisposition to Disease; Goals; Habits; Impairment; Implant; Impulsivity; Indiana; Individual; Individual Differences; Institution; Insula of Reil; Intake; Interoception; Journals; Learning; Link; Measures; Mediating; Mentors; Methods; Milk; Modeling; Molds; Motivation; Mus; Neurons; Neurosciences; Norepinephrine; Oral; Pathologic; Pattern; Performance; Phase; Phenotype; Play; Populations at Risk; Positioning Attribute; Preparation; Principal Component Analysis; Publishing; Reaction Time; Research; Research Personnel; Resources; Rewards; Risk; Rodent; Role; Signal Transduction; Silicon; Supervision; System; Techniques; Testing; Therapeutic; Training; Universities; Water; Work; alcohol behavior; alcohol exposure; alcohol research; alcohol reward; alcohol risk; alcohol seeking behavior; alcohol use disorder; awake; career; career development; cingulate cortex; density; design; drinking; endophenotype; experimental study; genetic manipulation; in vivo; interest; locus ceruleus structure; male; neural; neural circuit; neuroadaptation; neuromechanism; noradrenergic; novel therapeutic intervention; posters; preference; premature; reinforcer; response; success; sugar; symposium; therapeutic target; trait impulsivity; vigilance

Project Summary The primary training objective of the K99 phase of this award application is to mold the candidate into an expert in assessing behavioral engagement for reward using advanced in vivo electrophysiology methods. He will learn required analytical techniques for comprehensively measuring aspects of behavioral engagement and correlated brain activity patterns. The overarching hypothesis of this proposal is that Locus Coeruleus-cortical circuits regulate engagement when responding for alcohol, which is increased by protracted alcohol drinking. To address this hypothesis, this award will use Cambridge NeuroTech high-density silicon probes to record neural activity within the anterior cingulate cortex (ACC) and anterior insula (aINS), and also will use chemogenetic manipulation of noradrenaline signaling, during the 5-choice serial reaction time task (5-CSRTT) in mice responding for alcohol. During the K99 phase, the candidate will be trained in the use of high-density probes to generate large neural recording data sets to discover the relationship of ACC and aINS activity to behavioral engagement for sugar within the 5-CSRTT (a robust and widely used model). To obtain this training, the candidate will work with leading researchers at Indiana University with expertise in neural recording implementation and analyses. During the R00 phase, the candidate will use his recently published paradigm of behavioral engagement for alcohol in 5-CSRTT combined with K99 training to further support his hypothesis. Critical goals of this award are publishing results in high-impact journals, oral and poster presentations at conferences and attending relevant seminars to further the candidate’s career development and exposure within neuroscience/alcohol research community. In this proposal, Drs. Frederic Hopf, Christopher Lapish, Catharine Winstanley, Brian Mathur, and Nicholas Grahame will form a dedicated mentoring team for the candidate. Combined, these individuals hold expertise in relevant rodent behavior, in vivo electrophysiology in awake animals, alcohol research, noradrenaline signaling, and relevant cortical regions investigated in this proposal. The Indiana Alcohol Research Center, a collaboration between Indiana University and Indiana University-Purdue University-Indianapolis, provides a nationally recognized research environment with the resources necessary to complete the Aims within this proposal, as well as an exceptional mentoring environment. At the end of the K99 phase, the candidate will be seeking a faculty position as an independent investigator at an institution well-suited to for his R00 phase. The experiments in these studies will provide valuable groundwork for future R01 applications that will incorporate methods for projection-specific circuit inhibition and explore potential therapeutic avenues to attenuate maladaptive alcohol-engagement behaviors for future clinical benefit. Together, this award will provide a strong foundation for the candidate to build a successful career as an independent researcher within the alcohol field and contribute to the forward progress needed for combating problem alcohol use.

项目摘要 该奖项申请的K99阶段的主要培训目标是将候选人塑造成一个 使用先进的体内电生理方法评估行为参与的实验。他 将学习所需的分析技术，以全面衡量行为参与的各个方面 相关的大脑活动模式。该提议的总体假设是层层层层。 回应酒精时，电路会调节参与度，而饮酒会增加。 为了解决这一假设，该奖项将使用剑桥神经技术高密度硅问题记录 前扣带回皮质（ACC）和前岛（AINS）内的神经活动，也将使用 在5个选择的串行反应时间任务（5-CSRTT）期间，去甲肾上腺素信号传导的化学发生操作 在小鼠中回应酒精。在K99阶段，候选人将接受高密度使用 生成大型神经记录数据集的问题，以发现ACC和AINS活动与 5-CSRTT中糖的行为参与（强大而广泛的模型）。为了获得此培训， 候选人将与印第安纳大学的主要研究人员合作，并具有神经记录方面的专业知识 实施和分析。在R00阶段，候选人将使用他最近出版的范式 5-CSRTT中酒精的行为参与与K99培训相结合，以进一步支持他的假设。 该奖项的关键目标是在高影响期刊，口头和海报演示中发布结果 会议和参加相关的半手，以进一步促进候选人的职业发展和曝光 在神经科学/酒精研究社区中。在此提案中，博士。弗雷德里克·霍夫（Frederic Hopf），克里斯托弗·拉皮什（Christopher Lapish）， 凯瑟琳·温斯坦利（Catharine Winstanley），布莱恩·马修（Brian Mathur）和尼古拉斯·格雷厄姆（Nicholas Grahame）将组建一支专门的心理团队 候选人。这些人合并在相关的啮齿动物行为方面拥有专业知识，体内电生理学 在此研究的清醒动物，酒精研究，去甲肾上腺素信号传导和相关皮质区域 提议。印第安纳州酒精研究中心，印第安纳大学与印第安纳州之间的合作 大学普渡大学 - 印度波利斯大学，提供全国认可的研究环境 在本提案中完成目标所必需的资源以及出色的心理 环境。在K99阶段结束时，候选人将寻求教师职位 一家非常适合R00阶段的机构的调查员。这些研究的实验将提供 未来R01应用程序的价值基础，该应用程序将包含投影特异性电路的方法 抑制和探索潜在的治疗途径，以减轻适应不良的酒精参与行为 为了将来的临床益处。该奖项将为候选人建立一个奖项，为候选人提供坚实的基础 作为酒精领域的独立研究人员的成功职业生涯，并为前进的进步做出了贡献 打击问题的饮酒所需。