Targeted Circuit Manipulation for Ameliorating Huntington's Disease Pathogenesis

项目摘要/摘要 多样性补充候选人将接受关于操纵射击活动的所有方面的培训 通过化学生成抑制锥体神经元的皮质-纹状体微电路，测试抑制的效果 活体电生理记录，并在行为测试中评估这些操作是否在发病前 症状的减少将减缓HD疾病的进展。培训包括立体定向注射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，并分析收集到的数据。实验方法将允许应聘者评估 在这个明确定义的实验范例中，新的抑制性发光素的有效性，同时建立一个固体 为他未来在生物医学研究中的活动奠定了概念和实验基础。 应聘者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。培训计划考虑到应聘者正处于非常重要的位置 开始他的研究训练，并确保候选人将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活体实验的实践经验到 对收集到的数据进行评估和解释。因此，这种在活体电生理和行为方面的训练 测试不仅对父母的资助有很大的贡献，而且还将特别为他提供经验 需要追求他作为内科科学家的职业生涯的长期兴趣。 考虑到应聘者的职业阶段和未来计划，申请表中概述的拟议培训是理想的 是为在尽可能短的时间内产生最大影响而量身定做的。一项既定的培训战略将 培养候选人迅速达到能够独立处理新项目的能力，并将 成为他继续接受培训的任何研究实验室的资产。 拟议的补充活动将在原范围内增加父奖项的整体影响 奖励，同时推进候选人的培训和职业发展。

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.