Correlative study using structural MRI and super-resolution microscopy to detect structural alterations induced by long-term optogenetic stimulation of striatal medium spiny neurons
Correlative study using structural MRI and super-resolution microscopy to detect structural alterations induced by long-term optogenetic stimulation of striatal medium spiny neurons
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DOI：
10.1016/j.neuint.2019.02.017
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发表时间：
2019-05-01
影响因子：
4.2
通讯作者：
Tanaka, Kenji F.
中科院分区：
文献类型：
--
作者：
Abe, Yoshifumi;Komaki, Yuji;Tanaka, Kenji F.
纹状体中棘神经元（MSNs）控制运动功能。msn的高活性或低活性与基底神经节相关的运动障碍一致。基于神经元活动的持续变化导致大脑结构变化的假设，了解这些结构变化可能用于推断MSN功能异常。为了从结构数据推断MSN的功能，了解MSN活动的长期变化如何影响大脑形态是必不可少的。为了解决这个问题，我们利用了一个简化的模型，通过刺激表达通道视紫红质2 （ChR2）的msn来诱导功能。通过扩散张量成像（DTI）和超分辨率显微镜组织学评估，研究了纹状体通路及其相关区域随后的结构改变，这些结构改变导致了这些msn的长期活性变化。DTI检测到纹状体、黑质和运动皮层的变化。组织学检查发现髓鞘皮质轴突以及MSN树突和轴突的直径减少。结构变化显示DTI参数与组织学数据高度相关。这些结果表明，长期的神经激活改变了单胞核和皮质神经元纤维的直径。这项研究为理解功能和结构改变之间的因果关系提供了一个工具。
Striatal medium spiny neurons (MSNs) control motor function. Hyper- or hypo-activity of MSNs coincides with basal ganglia-related movement disorders. Based on the assumption that lasting alterations in neuronal activity lead to structural changes in the brain, understanding these structural alterations may be used to infer MSN functional abnormalities. To infer MSN function from structural data, understanding how long-lasting alterations in MSN activity affect brain morphology is essential. To address this, we utilized a simplified model of functional induction by stimulating MSNs expressing channelrhodopsin 2 (ChR2). Subsequent structural alterations which induced long-term activity changes in these MSNs were investigated in the striatal pathway and its associated regions by diffusion tensor imaging (DTI) and histological assessment with super-resolution microscopy. DTI detected changes in the striatum, substantia nigra, and motor cortex. Histological assessment found a reduction in the diameter of myelinated cortical axons as well as MSN dendrites and axons. The structural changes showed a high correlation between DTI parameters and histological data. These results demonstrated that long-term neural activation in the MSNs alters the diameter of MSN and cortical neurons fibers. This study provides a tool for understanding the causal relationship between functional and structural alterations.