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: 10766877
• 负责人: Nicholas M Timme
• 金额: $ 5.76万
• 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: 2023-01-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10766877
• 关键词: Address; Administrative Supplement; Affect; Alcohol consumption; Alcohols; Applications Grants; Appointment; Aversive Stimulus; Award; Biological; Brain; Brain region; COVID-19 pandemic effects; Cell physiology; Collaborations; Data Set; Decision Making; Disease; Educational workshop; Electrophysiology (science); Environment; Faculty; Financial Support; Foundations; Fright; Future; Goals; Head; Individual; International; Intervention; Journals; Laboratories; Mentors; Mus; Neurons; Parents; Persons; Phase; Positioning Attribute; Preparation; Process; Publishing; Research; Research Personnel; Resources; Rewards; Risk; Route; System; Techniques; Time; Training; Work; alcohol research; alcohol risk; alcohol use disorder; brain cell; career; career development; computational neuroscience; density; experimental study; improved; neural; neural circuit; neural correlate; novel; sex; symposium; tool

Project Summary Administrative Supplement Summary: The purpose of this administrative supplement is to provide additional financial support in order to allow for more time to complete the original goals of the parent K99/R00 award. This additional time is necessary due to the impacts of the Covid-19 pandemic (please see Introduction to the Supplement document for full justification). The scientific and career development goals of the supplement are identical to the original project. During this supplemental time period, Dr. Timme will conduct crucial experiments outlined in the original proposal (specifically, pilot head-fixed electrophysiological recordings) and continue to pursue faculty appointments. Original 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 行政补充摘要：此行政补充的目的是提供额外 财政支持，以便有更多时间完成家长K99/R00奖的原始目标。这 由于COVID-19大流行的影响，需要额外的时间（请参阅介绍 补充文件以完全理由）。补充的科学和职业发展目标是 与原始项目相同。在此补充时期，Timme博士将进行关键实验 在原始建议中概述（特别是试验性头部固定电生理记录） 追求教师任命。 原始项目摘要：该K99/R00应用程序的K99阶段的主要培训目标是 为候选人提供最先进的电生理技术培训，以准备职业 酒精研究领域的独立研究者。该提议的总体假设是 酒精使用障碍（AUD）的决策故障是由同意的神经活动变化引起的 在多个关键的大脑区域中，这些区域可以通过不同的电路将决策过程路由。解决 这个假设，该奖项将使用高密度神经问题来记录数百种的电活动 决定喝酒期间，许多大脑区域的神经元。候选人将获得 使用这些神经探针来生成大型神经记录数据集的必要培训 用于直接观察到AUD中决策故障的神经回路的变化。到 获得这种必要的培训，候选人将与已经在使用这些工具的领先研究人员合作 国际脑实验室合作并参加培训研讨会。候选人的职业发展 还将通过在高影响期刊上发布结果，参加会议并参加相关的结果来进一步进一步 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·霍夫夫（Woody Hopf）博士。 Susan Sangha，Kenneth Harris博士和David Kareken博士。这些人是系统专家， 计算神经科学，恐惧和奖励的神经元电路，酒精研究，头部固定小鼠研究， 和性作为生物学变量。 IUPUI的长期合作研究环境将提供 候选人拥有必要的资源来完成本提案中概述的目标。在结束时 奖项的K99阶段，候选人将寻求教师职位作为独立调查员的职位 奖励的R00阶段的开始。在这个新职位上，研究将扩展到包括中性 厌恶刺激的相关性，以便更好地理解继续饮酒的决定 负面后果。这项工作将导致候选人与进一步有关的R01赠款申请 记录和神经回路的干预措施以治疗故障决策。通过确定变化 这项研究将指导未来的研究，该研究旨在 为那些患有AUD或有风险的人开发新的治疗方法。该奖项将奠定基础 对于酒精研究的独立职业，有可能大大改善人们的生活 受这种疾病的影响。