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.

项目总结