Limbic-basal ganglia connectivity in a non-human primate model of Huntington's disease

亨廷顿病（HD）是一种由CAG重复序列扩增引起的退行性神经系统疾病 4号染色体上显性遗传的HTT基因中的序列。当CAG重复拉伸超过40 重复编码的突变亨廷顿蛋白（mHTT）错误折叠，导致功能的毒性获得， 神经退化HD症状对患者的生活质量有害，因为他们患有 进行性多动性运动障碍，伴有认知功能恶化， 性格变化/情绪紊乱。病人和病人的情绪和身体负担 照顾者是巨大的，病人经常报告他们的情绪症状是最沉重的负担， 他们自己和他们的照顾者。为了满足这一需求，我的项目的中心目标将是描述 HD神经病理学对边缘-基底神经节连接性和相关行为表型的影响 情绪/精神症状。我将使用行为分析来评估我们的HD动物模型的情绪和影响， 我将进行神经成像，组织学和分子分析，专注于感兴趣的特定区域， 边缘系统（杏仁核、前扣带皮层、眶额皮层）和基底神经节（尾状核和壳核） 地区总之，我将采取多方面的方法，使用体内（神经成像和行为测定）， 目的1和2）和离体（目的3中的组织学和分子学）技术。我学习的优势在于 他们识别可能与各种行为相关的前瞻性神经影像学变化的能力， 和HD的神经病理表型。

Huntington's disease (HD) is a degenerative neurological disorder caused by an expanded CAG repeat sequence in the dominantly-inherited HTT gene on chromosome 4. When the CAG repeat stretch exceeds 40 repeats the encoded mutant huntingtin protein (mHTT) misfolds, resulting in a toxic gain of function that is neurodegenerative. HD symptoms are detrimental to the patient's quality of life, as they suffer from a progressive hyperkinetic movement disorder accompanied by deteriorating cognitive function and profound personality changes/mood disturbances. The emotional and physical burden on both the patient and the caregiver are tremendous, and patients often report their mood symptoms to be the most burdensome to both themselves and their caretakers. To address this need, the central goal of my project will be to characterize the impact of HD neuropathology on limbic-basal ganglia connectivity and behavioral phenotypes relevant to the mood/psychiatric symptoms. I will use behavioral assays to assess mood and affect in our HD animal model, and I will perform neuroimaging, histological, and molecular analyses, focusing on specific regions of interest in limbic (amygdala, anterior cingulate cortex, orbitofrontal cortex) and basal ganglia (caudate and putamen) regions. In sum, I will take a multifaceted approach using both in vivo (neuroimaging and behavioral assays in Aim 1 and 2) and ex vivo (histological and molecular in Aim 3) techniques. The strength of my studies lays in their ability to identify prospective neuroimaging changes that can be connected with a wide array of behavioral and neuropathological phenotypes of HD.