Cerebellar Premotor Output Neurons Collateralize to Innervate the Cerebellar Cortex.
Cerebellar Premotor Output Neurons Collateralize to Innervate the Cerebellar Cortex.
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DOI：
10.1002/cne.23787
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发表时间：
2015-10-15
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通讯作者：
Person AL
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作者：
Houck BD;Person AL
由小脑计算的运动指令被假设为使用推论放电或传出指令的副本来加速运动矫正。因此，确定必然放电的来源对于检验这一假说至关重要。在这里，我们验证了小鼠小脑核到小脑皮质的通路包括小脑运动前输出神经元的侧支，绘制了这条侧支通路，并确定了其突触后靶点。在将示踪剂双向注射到小脑核团的远端靶点丘脑腹外侧部后，我们在小脑核团中观察到逆行标记的胞体，并在小脑颗粒层观察到苔藓纤维终末，这与侧支一致。双向示踪剂注射到小脑皮质，逆行标记了小脑核和丘脑腹外侧部的胞体，证实了这些观察结果。为了测试投射到红核的核输出神经元是否也侧支到小脑皮质，我们使用了依赖CRE的病毒方法，避免了直接投射红核到小脑的潜在混淆。将依赖于Cre的绿色荧光蛋白表达病毒注射到Ntsr1-Cre小鼠体内，这种病毒选择性地在小脑核表达Cre，在插入的核中逆行标记的胞体，以及假定的侧枝在小脑皮质终止为苔藓纤维。所有标记的苔藓纤维终末的突触后靶标用免疫组织化学高尔基体细胞标记物和颗粒细胞的电子显微镜特征进行了识别，表明核输出神经元的侧支同时接触高尔基体细胞和颗粒细胞。这些结果阐明了核皮质投射的一个子集的组织，这些投射构成了小脑内实验上可获得的必然放电途径。
Motor commands computed by the cerebellum are hypothesized to use corollary discharge, or copies of outgoing commands, to accelerate motor corrections. Identifying sources of corollary discharge, therefore, is critical for testing this hypothesis. Here, we verified that the pathway from the cerebellar nuclei to the cerebellar cortex in mice includes collaterals of cerebellar premotor output neurons, mapped this collateral pathway, and identified its postsynaptic targets. Following bidirectional tracer injections into a distal target of the cerebellar nuclei, the ventrolateral thalamus, we observed retrogradely labeled somata in the cerebellar nuclei and mossy fiber terminals in the cerebellar granule layer, consistent with collateral branching. Corroborating these observations, bidirectional tracer injections into the cerebellar cortex retrogradely labeled somata in the cerebellar nuclei and boutons in the ventrolateral thalamus. To test whether nuclear output neurons projecting to the red nucleus also collateralize to the cerebellar cortex, we used a Cre-dependent viral approach, avoiding potential confounds of direct red nucleus-to-cerebellum projections. Injections of a Cre-dependent GFP-expressing virus into Ntsr1-Cre mice, which express Cre selectively in the cerebellar nuclei, retrogradely labeled somata in the interposed nucleus and putative collateral branches terminating as mossy fibers in the cerebellar cortex. Postsynaptic targets of all labeled mossy fiber terminals were identified using immunohistochemical Golgi cell markers and electron microscopic profiles of granule cells, indicating that the collaterals of nuclear output neurons contact both Golgi and granule cells. These results clarify the organization of a subset of nucleocortical projections which constitute an experimentally accessible corollary discharge pathway within the cerebellum.