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.

项目概要 该 K99/R00 应用程序 K99 阶段的主要培训目标是为候选人提供 最先进的电生理学技术培训，为独立调查员的职业生涯做好准备 在酒精研究领域。该提案的总体假设是决策失灵 酒精使用障碍 (AUD) 是由多个关键大脑区域同时发生的神经活动变化引起的，这些变化 用于通过不同的电路来路由决策过程。为了解决这一假设，该奖项将 使用高密度神经探针记录多个大脑区域数百个神经元的电活动 头部固定的小鼠在决定饮酒期间。候选人将接受必要的使用培训 这些神经探针生成大型神经记录数据集，可用于直接观察变化 澳元决策故障背后的神经回路。为了获得这种必要的培训， 候选人将与国际脑实验室已经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得到进一步促进 在高影响力期刊上发表成果、参加会议以及参加相关的校园研讨会。 拟议的指导团队包括 Christopher Lapish 博士、Woody Hopf 博士、Susan Sangha 博士、Kenneth 博士 哈里斯和大卫·卡里肯博士。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 的长期合作研究环境将为候选人提供必要的条件 资源来完成本提案中概述的目标。在 K99 奖项阶段结束时， 候选人将在 R00 阶段开始时寻求作为独立研究者的教职职位 的奖项。在这个新的位置上，研究将扩大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 该工作将导致候选人申请与神经系统进一步录音和干预相关的 R01 拨款申请 处理故障决策的电路。通过识别潜在神经回路的变化 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 那些患有澳元或有澳元风险的人。该奖项将为以后的独立职业生涯奠定基础 酒精研究有可能大大改善受这种疾病影响的人们的生活。