Mossy Fibers Terminate Directly Within Purkinje Cell Zones During Mouse Development.
Mossy Fibers Terminate Directly Within Purkinje Cell Zones During Mouse Development.
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DOI：
10.1007/s12311-015-0712-6
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发表时间：
2016-02
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影响因子：
--
通讯作者：
Sillitoe RV
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作者：
Sillitoe RV
小脑被组织成一张区域图，根据基因表达、解剖连接性、神经元放电特性、行为特异性和对疾病的易感性以各种方式表现出来。每个区域的中心是浦肯野细胞，它是小脑的主要细胞类型，也是小脑皮质的唯一输出。在发育过程中，浦肯野细胞被认为协调所有其他细胞类型的区域模式。然而，介导浦肯野细胞和传入纤维之间相互作用的形态发生机制仍不清楚。为了在体内解决这个问题，我利用基于荧光的快速突触追踪方法来确定出生后早期发育期间苔藓纤维与浦肯野细胞连接的性质，这是传入图组装成清晰的区域回路的时期。通过将 WGA-Alexa 555 注射到下胸段-上腰段脊髓，我发现脊髓小脑苔藓纤维通过突触将示踪剂转移到与纤维直接相邻的浦肯野细胞区域。追踪到的浦肯野细胞区域形成了类似斑马蛋白的模式，该模式由神经丝重链（NFH）的表达来定义，NFH是出生后发育中小脑区域的标记。这些结果表明浦肯野细胞通过使用分子线索、神经元活动和突触接触来生成区域电路图。
The cerebellum is organized into a map of zones that is manifested in various ways according to gene expression, anatomical connectivity, neuronal firing properties, behavioral specificity, and susceptibility to disease. At the center of every zone is the Purkinje cell, the principal cell type of the cerebellum and sole output of the cerebellar cortex. During development, Purkinje cells are thought to coordinate the zonal patterning of all other cell types. However, the morphogenetic mechanism that mediates the interaction between Purkinje cells and afferent fibers remains unclear. To address this problem in vivo, I took advantage of a rapid fluorescent-based transynaptic tracing approach to determine the nature of mossy fiber to Purkinje cell connectivity during early postnatal development, a period when the afferent map is assembling into clear-cut zonal circuits. By injecting WGA-Alexa 555 into the lower thoracic-upper lumber spinal cord, I found that spinocerebellar mossy fibers transynaptically transfer tracer into zones of Purkinje cells that are directly adjacent to the fibers. The traced Purkinje cell zones formed a zebrin-like pattern that was defined by the expression of neurofilament heavy chain (NFH), a marker of zones in the postnatal developing cerebellum. These results suggest that Purkinje cells generate the zonal circuit map by using molecular cues, neuronal activity, and synaptic contact.