Identifying how alcohol-evoked changes in neural firing affect systems level computations during decision-making

确定酒精引起的神经放电变化如何影响决策过程中的系统级计算

• 批准号: 10368116
• 负责人: Nicholas M Timme
• 金额: $ 16.13万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-10 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10368116
• 关键词: Acclimatization; Address; Affect; Alcohol consumption; Alcohols; Animals; Anterior; Applications Grants; Area; Aversive Stimulus; Award; Behavior; Behavioral; Biological; Blood; Brain; Brain region; Cell physiology; Cells; Collaborations; Cues; Data; Data Set; Decision Making; Discrimination; Disease; Educational workshop; Electrophysiology (science); Environment; Ethanol; Exhibits; Faculty; Foundations; Fright; Future; Goals; Head; Impairment; Individual; International; Intervention; Journals; Laboratories; Lead; Medial; Mentors; Modification; Mus; Neurobiology; Neurons; Pathology; Pattern; Performance; Persons; Pharmacology; Phase; Population; Positioning Attribute; Prefrontal Cortex; Preparation; Process; Publishing; Quinine; Research; Research Personnel; Resistance; Resolution; Resources; Rewards; Risk; Route; Signal Transduction; Synapses; System; Task Performances; Techniques; Testing; Time; Training; Ventral Striatum; Visual; Water; Work; alcohol abuse therapy; alcohol effect; alcohol exposure; alcohol research; alcohol reward; alcohol risk; alcohol use disorder; brain cell; career; career development; computational neuroscience; density; drinking; experimental study; flexibility; improved; insight; neural circuit; neural correlate; neurophysiology; neurotransmission; novel; reinforcer; relating to nervous system; repaired; sex; symposium; theories; tool

Project Summary The primary training objective of the K99 phase of this K99/R00 application is to provide the candidate with training in state-of-the-art electrophysiology techniques in preparation for a career as an independent investigator in the field of alcohol research. The overarching hypothesis of this proposal is that decision-making malfunctions in alcohol use disorder (AUD) are caused by concurring neural activity changes in multiple key brain regions that serve to route the decision-making process through different circuits. To address this hypothesis, this award will use high-density neural probes to record the electrical activity of hundreds of neurons across many brain regions in head-fixed mice during the decision to drink. The candidate will obtain the necessary training in the use of these neural probes to generate large neural recording data sets that can be used to directly observe changes in the neural circuits underlying malfunctioning decision-making in AUD. To obtain this necessary training, the candidate will work with leading researchers already using these tools in the International Brain Laboratory collaboration and attend a training workshop. The candidate’s career development will also be furthered by publishing results in high-impact journals, attending conferences, and attending relevant on-campus seminars. The proposed mentoring team includes Dr. Christopher Lapish, Dr. Woody Hopf, Dr. Susan Sangha, Dr. Kenneth Harris, and Dr. David Kareken. These individuals are experts in systems and computational neuroscience, the neural circuitry of fear and reward, alcohol research, head-fixed mouse studies, and sex as a biological variable. The long-standing collaborative research environment at IUPUI will provide the candidate with the necessary resources to complete the aims as outlined in this proposal. During the end of the K99 phase of the award, the candidate will seek out a faculty position as an independent investigator to begin at the start of the R00 phase of the award. In this new position, the studies will expand to include the neural correlates of aversive stimuli in order to better understand the decision to continue drinking alcohol in the face of negative consequences. This work will lead to R01 grant applications by the candidate related to further recordings and interventions in neural circuits to treat malfunctioning decision-making. By identifying changes in the neural circuits underlying malfunctioning decision-making, this research will guide future studies that seek to develop novel treatments for those people suffering from or at risk for AUD. This award will lay the foundation for an independent career in alcohol research which has the potential to greatly improve the lives of people impacted by this disease.

项目摘要 本K99/R 00应用程序的K99阶段的主要培训目标是为候选人提供 接受最先进的电生理学技术培训，为独立调查员的职业生涯做准备 在酒精研究领域。这一建议的首要假设是，决策失灵 酒精使用障碍（AUD）是由多个关键脑区同时发生神经活动变化引起的， 通过不同的回路来引导决策过程。为了解决这一假设，该奖项将 使用高密度神经探针记录大脑多个区域数百个神经元的电活动 在决定喝水的过程中，候选人将获得使用 这些神经探测器生成可用于直接观察变化的大型神经记录数据集 在AUD中的决策故障的神经回路中。为了获得这种必要的培训， 候选人将与已经在国际脑实验室使用这些工具的领先研究人员一起工作 合作，参加培训班。候选人的职业发展也将得到进一步的 在高影响力的期刊上发表成果，参加会议，并参加相关的校园研讨会。 拟议的指导小组包括克里斯托弗·拉皮什博士、伍迪·霍普夫博士、苏珊·桑加博士、肯尼思博士 哈里斯和大卫·卡雷肯博士。这些人是系统和计算神经科学的专家， 恐惧和奖励的神经回路，酒精研究，头部固定小鼠研究，以及性别作为生物变量。 IUPUI长期的合作研究环境将为候选人提供必要的 资源，以完成本提案中概述的目标。在K99阶段结束时， 候选人将寻找一个教师职位作为一个独立的调查员，开始在R 00阶段的开始 获奖名单在这个新的位置，研究将扩大到包括神经相关的厌恶刺激， 为了更好地理解在面对负面后果时继续饮酒的决定。这 工作将导致R 01赠款申请的候选人有关的进一步记录和干预，在神经 治疗决策失误的电路。通过识别潜在的神经回路的变化 决策失误，这项研究将指导未来的研究，寻求开发新的治疗方法， 患有或有风险患上澳元的人士。该奖项将为独立的职业生涯奠定基础， 酒精研究有可能大大改善受这种疾病影响的人的生活。