Barry Joshua, Peng Allison, Levine Michael S, Cepeda Carlos
Intellectual and Developmental Disabilities Research Center (IDDRC), Semel Institute for Neuroscience and Human Behavior, Jane and Terry Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States.
Front Neurosci. 2022 Nov 3;16:1040113. doi: 10.3389/fnins.2022.1040113. eCollection 2022.
Huntington's disease (HD) is a fatal, hereditary neurodegenerative disorder that causes chorea, cognitive deficits, and psychiatric symptoms. It is characterized by accumulation of mutant Htt protein, which primarily impacts striatal medium-sized spiny neurons (MSNs), as well as cortical pyramidal neurons (CPNs), causing synapse loss and eventually cell death. Perturbed Ca homeostasis is believed to play a major role in HD, as altered Ca homeostasis often precedes striatal dysfunction and manifestation of HD symptoms. In addition, dysregulation of Ca can cause morphological and functional changes in MSNs and CPNs. Therefore, Ca imaging techniques have the potential of visualizing changes in Ca dynamics and neuronal activity in HD animal models. This minireview focuses on studies using diverse Ca imaging techniques, including two-photon microscopy, fiber photometry, and miniscopes, in combination of Ca indicators to monitor activity of neurons in HD models as the disease progresses. We then discuss the future applications of Ca imaging to visualize disease mechanisms and alterations associated with HD, as well as studies showing how, as a proof-of-concept, Caimaging using miniscopes in freely-behaving animals can help elucidate the differential role of direct and indirect pathway MSNs in HD symptoms.
亨廷顿舞蹈症（HD）是一种致命的遗传性神经退行性疾病，会导致舞蹈症、认知缺陷和精神症状。其特征是突变型亨廷顿蛋白（Htt）的积累，这主要影响纹状体中型多棘神经元（MSN）以及皮质锥体神经元（CPN），导致突触丧失并最终导致细胞死亡。钙稳态失调被认为在HD中起主要作用，因为钙稳态改变通常先于纹状体功能障碍和HD症状的出现。此外，钙的失调会导致MSN和CPN的形态和功能变化。因此，钙成像技术有潜力可视化HD动物模型中钙动力学和神经元活动的变化。本综述聚焦于使用多种钙成像技术的研究，包括双光子显微镜、光纤光度法和微型显微镜，结合钙指示剂来监测HD模型中神经元在疾病进展过程中的活动。然后，我们讨论了钙成像在可视化与HD相关的疾病机制和改变方面的未来应用，以及一些研究，这些研究表明，作为概念验证，在自由活动的动物中使用微型显微镜进行钙成像有助于阐明直接和间接通路MSN在HD症状中的不同作用。
