Targeted Circuit Manipulation for Ameliorating Huntington's Disease Pathogenesis

改善亨廷顿病发病机制的靶向电路操作

• 批准号: 10841909
• 负责人: UTE H HOCHGESCHWENDER
• 金额: $ 1.5万
• 依托单位: CENTRAL MICHIGAN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10841909
• 关键词: Acute; Address; Award; BRAIN initiative; Behavior; Behavioral; Biomedical Research; Collaborations; Corpus striatum structure; Data; Data Analyses; Development; Disease Progression; Disease model; Electrophysiology (science); Ensure; Fostering; Foundations; Future; Genetic; Goals; Huntington Disease; Injections; Intervention; National Institute of Mental Health; National Institute of Neurological Disorders and Stroke; Neurodegenerative Disorders; Neurons; Neurosciences; Parents; Pathogenesis; Phase; Physicians; Research; Research Personnel; Research Training; Scientist; Solid; Symptoms; Time; Training; Transgenic Mice; behavior test; career; career development; efficacy evaluation; efficacy testing; experience; experimental study; extracellular; hippocampal pyramidal neuron; in vivo; interest; meetings; mouse model; neural circuit; neuroregulation; novel; novel strategies; novel therapeutics; parent grant; prevent; tool; translational progress

PROJECT SUMMARY/ABSTRACT The Diversity Supplement candidate will be trained in all aspects of manipulating the firing activity within the cortico-striatal microcircuit by chemogenetic inhibition of pyramidal neurons, testing efficacy of inhibition by electrophysiological recordings in vivo, and assessing in behavioral tests if these manipulations before the onset of symptoms will slow HD disease progression. The training includes stereotaxic injections of AAV, acute extracellular recordings and computational electrophysiological data analysis, and conducting behavioral test batteries and analyzing the collected data. The experimental approach will allow the candidate to assess the efficacy of novel inhibitory luminopsins within this well-defined experimental paradigm while building a solid conceptual and experimental foundation for his future activities in biomedical research. The training experiences the candidate will gain are critical for his understanding and interpretation of state-of- the-art neuroscience experiments. The training plan takes into consideration that the candidate is at the very beginning of his research training and ensures that the candidate will have an exceedingly strong background for entering the next phase of research training towards meeting his career goals. His training will have ranged from hands-on experience in executing in vivo experiments for controlling neural activity and behavior to evaluating and interpreting the collected data. Therefore, this training in in vivo electrophysiology and behavior testing will not only significantly contribute to the parent grant but will specifically provide him the experience required to pursue his long-term interest in pursuing a career as a physician-scientist. The proposed training outlined in the application is ideal given the candidate’s career stage and future plans and is tailored to having the greatest impact within th ehsortest possible time. An established training strategy will foster the candidate’s ability to swiftly reach a level where he can independently approach new projects and will be an asset to any research lab where he continues his training. The proposed supplement activities will increase the parent award’s overall impact within the original scope of award while at the same time advancing the training and career development of the candidate.

项目概要/摘要 多样性补充候选人将接受在操纵射击活动的各个方面的培训 通过化学遗传学抑制锥体神经元的皮质纹状体微电路，测试抑制效果 体内电生理记录，并在行为测试中评估这些操作是否在发病前进行 症状将减缓 HD 疾病的进展。培训内容包括AAV立体定位注射、急性 细胞外记录和计算电生理数据分析，并进行行为测试 电池并分析收集的数据。实验方法将允许候选人评估 在这个明确的实验范式中，新型抑制性发光蛋白的功效，同时建立了坚实的基础 为他未来的生物医学研究活动奠定了概念和实验基础。 候选人将获得的培训经验对于他理解和解释现状至关重要 最先进的神经科学实验。培训计划考虑到候选人处于最 研究培训的开始，并确保候选人拥有非常强大的背景 进入下一阶段的研究培训，以实现他的职业目标。他的训练范围很广 从执行控制神经活动和行为的体内实验的实践经验到 评估和解释收集到的数据。因此，这种体内电生理学和行为学的训练 测试不仅会为家长补助金做出重大贡献，而且会特别为他提供经验 需要追求他作为一名医师科学家职业的长期兴趣。 考虑到候选人的职业阶段和未来计划，申请中概述的拟议培训是理想的 旨在在尽可能短的时间内产生最大的影响。既定的培训策略将 培养候选人迅速达到能够独立处理新项目并愿意的水平的能力 对他继续接受培训的任何研究实验室来说都是一笔财富。 拟议的补充活动将在原有范围内增加家长奖的整体影响 奖项，同时促进候选人的培训和职业发展。