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/文摘