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; 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 该K99/R00应用的K99阶段的主要培训目标是为候选人提供 在最先进的电生理学技术中培训，以准备作为独立研究者的职业 在酒精研究领域。该提议的总体假设是决策故障 在酒精使用障碍（AUD）中是由多个关键大脑区域的神经活动变化引起的 服务以通过不同的电路路由决策过程。为了解决这一假设，该奖项将 使用高密度的神经元问题记录许多大脑区域的数百个神经元的电活动 在决定喝酒期间，在头部固定的小鼠中。候选人将获得使用的必要培训 这些神经探针生成大型神经元记录数据集，可用于直接观察变化 在AUD中的决策故障的基础神经回路中。为了获得这种必要的培训， 候选人将与已经在国际大脑实验室中使用这些工具的领先研究人员合作 合作并参加培训研讨会。候选人的职业发展也将由 在高影响力期刊上发布结果，参加会议，并参加相关的校园中心。 拟议的指导团队包括克里斯托弗·拉皮什（Christopher Lapish）博士，伍迪·霍夫（Woody Hopf）博士，苏珊·桑哈（Susan Sangha）博士，肯尼斯（Kenneth）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领域的专家 恐惧和奖励，酒精研究，固定小鼠研究以及性别作为生物学变量的神经回路。 IUPUI的长期合作研究环境将为候选人提供必要的 如本提案中概述的资源以完成目标。在奖项的K99阶段结束时， 候选人将在R00阶段开始时寻找作为独立研究人员的教师职位 奖项。在这个新的位置，研究将扩展到包括厌恶刺激的神经相关性 为了更好地理解面对负面后果，继续饮酒的决定。这 工作将导致与其他录音和神经干预有关的候选人的R01赠款申请 电路以治疗故障决策。通过确定神经回路的变化 解决决策的故障，这项研究将指导未来的研究，试图开发新的治疗方法 那些遭受AUD或有风险的人。该奖项将为独立职业奠定基础 酒精研究有可能大大改善受这种疾病影响的人们的生活。