Department of Neuroscience, Erasmus Medical Center, 3015 AA Rotterdam, The Netherlands.
Department of Translational Neuroscience, MIND Facility, University Medical Center Utrecht Brain Center, University of Utrecht, 3584 CX Utrecht, The Netherlands.
Cells. 2022 Nov 27;11(23):3800. doi: 10.3390/cells11233800.
The main connection from cerebellum to cerebrum is formed by cerebellar nuclei axons that synapse in the thalamus. Apart from its role in coordinating sensorimotor integration in the adult brain, the cerebello-thalamic tract (CbT) has also been implicated in developmental disorders, such as autism spectrum disorders. Although the development of the cerebellum, thalamus and cerebral cortex have been studied, there is no detailed description of the ontogeny of the mammalian CbT. Here we investigated the development of the CbT at embryonic stages using transgenic mice and in utero electroporation of wild type mice. Wide-field, confocal and 3D light-sheet microscopy of immunohistochemical stainings showed that CbT fibers arrive in the prethalamus between E14.5 and E15.5, but only invade the thalamus after E16.5. We quantified the spread of CbT fibers throughout the various thalamic nuclei and found that at E17.5 and E18.5 the ventrolateral, ventromedial and parafascicular nuclei, but also the mediodorsal and posterior complex, become increasingly innervated. Several CbT fiber varicosities express vesicular glutamate transporter type 2 at E18.5, indicating cerebello-thalamic synapses. Our results provide the first quantitative data on the developing murine CbT, which provides guidance for future investigations of the impact that cerebellum has on thalamo-cortical networks during development.
小脑与大脑的主要连接是由小脑核轴突形成的，它们在丘脑处形成突触。除了在成人大脑中协调感觉运动整合方面的作用外，小脑-丘脑束（CbT）还与自闭症谱系障碍等发育障碍有关。尽管小脑、丘脑和大脑皮层的发育已经得到研究，但哺乳动物 CbT 的个体发生还没有详细描述。在这里，我们使用转基因小鼠和野生型小鼠的体内电穿孔技术，在胚胎阶段研究了 CbT 的发育。免疫组织化学染色的宽场、共聚焦和 3D 光片显微镜显示，CbT 纤维在 E14.5 和 E15.5 之间到达前丘脑，但仅在 E16.5 之后才侵入丘脑。我们量化了 CbT 纤维在各个丘脑核中的扩散情况，发现到 E17.5 和 E18.5 时，腹外侧、腹内侧和旁束核以及中背侧和后复合体逐渐被支配。几个 CbT 纤维膨体在 E18.5 时表达囊泡谷氨酸转运体 2，表明小脑-丘脑突触的存在。我们的研究结果提供了发育中的小鼠 CbT 的第一个定量数据，为未来研究小脑在发育过程中对丘脑-皮质网络的影响提供了指导。
