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.

项目概要 行政补充摘要：本行政补充的目的是提供额外的信息 资金支持，以便有更多时间完成母公司 K99/R00 奖项的原定目标。 由于 Covid-19 大流行的影响，需要额外的时间（请参阅简介） 完整论证的补充文件）。补充的科学和职业发展目标是。 与原始项目相同，在这段补充时间内，蒂姆博士将进行重要的实验。 原始提案中概述（特别是飞行员头部固定的电生理记录）并继续 寻求教师任命。 原始项目摘要：此 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学技术培训，为他们的职业生涯做好准备 酒精研究领域的独立研究者。该提案的总体假设是： 酒精使用障碍 (AUD) 的决策障碍是由同时发生的神经活动变化引起的 在多个关键大脑区域中，这些区域用于通过不同的电路来路由决策过程。 根据这一假设，该奖项将使用高密度神经探针来记录数百个的电活动 在做出饮酒决定期间，头部固定小鼠的许多大脑区域的神经元将获得。 使用这些神经探针生成大型神经记录数据集的必要培训 用于直接观察 AUD To 故障决策的神经回路的变化。 获得必要的培训后，候选人将与已经在该领域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候选人的职业发展培训研讨会。 还将通过在高影响力期刊上发表结果、参加会议和参加相关的活动来进一步推动 拟议的导师团队包括 Christopher Lapish 博士、Woody Hopf 博士、 Susan Sangha、Kenneth Harris 博士和 David Kareken 博士这些人都是系统和技术领域的专家。 计算神经科学、恐惧和奖励的神经回路、酒精研究、头部固定小鼠研究、 IUPUI 的长期合作研究环境将提供性别作为生物学变量。 候选人拥有必要的资源来完成本提案中概述的目标。 在该奖项的 K99 阶段，候选人将寻求作为独立调查员的教职职位，从 奖项 R00 阶段的开始 在这个新职位上，研究范围将扩大到包括神经网络。 厌恶刺激的相关性，以便更好地理解继续在脸上喝酒的决定 这项工作将导致候选人提出与进一步相关的 R01 拨款申请。 通过识别神经回路的变化来治疗决策故障。 神经回路是决策故障的基础，这项研究将指导未来的研究 该奖项将为患有 AUD 或有风险的患者开发新的治疗方法。 从事酒精研究的独立职业，有可能极大地改善人们的生活 受此病影响。