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.

项目总结/摘要 多样性补充候选人将接受操纵射击活动的各个方面的培训， 皮质-纹状体微电路通过锥体神经元的化学发生抑制，测试抑制的功效， 体内电生理记录，并在行为测试中评估这些操作是否在发作前 会减缓HD疾病的进展。培训包括立体定位注射AAV，急性 细胞外记录和计算电生理数据分析，并进行行为测试 电池和分析收集的数据。实验方法将允许候选人评估 新的抑制性发光蛋白在该明确定义的实验范例中的功效， 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他理解和解释国家的发展至关重要。 最先进的神经科学实验培训计划考虑到候选人在非常 开始他的研究培训，并确保候选人将有一个非常强大的背景 为实现他的职业目标进入下一阶段的研究培训。他的训练 从执行用于控制神经活动和行为的体内实验的实践经验， 评估和解释收集的数据。因此，这种在体电生理学和行为的训练 测试不仅会大大有助于家长补助金，但将专门为他提供的经验， 需要追求他的长期兴趣，追求职业生涯作为一个物理学家，科学家。 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， 是为了在最短的时间内产生最大的影响。既定的培训战略将 培养候选人的能力，使其迅速达到一个能够独立处理新项目的水平，并将 对他继续训练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的范围内增加家长奖的总体影响， 奖励，同时促进候选人的培训和职业发展。