Origin, lineage and function of cerebellar glia

Abstract

The glial cells of the cerebellum, and particularly astrocytes and oligodendrocytes, are characterized by a remarkable phenotypic variety, in which highly peculiar morphological features are associated with specific functional features, unique among the glial cells of the entire CNS. Here, we provide a critical report about the present knowledge of the development of cerebellar glia, including lineage relationships between cerebellar neurons, astrocytes and oligodendrocytes, the origins and the genesis of the repertoire of glial types, and the processes underlying their acquisition of mature morphological and functional traits. In parallel, we describe and discuss some fundamental roles played by specific categories of glial cells during cerebellar development. In particular, we propose that Bergmann glia exerts a crucial scaffolding activity that, together with the organizing function of Purkinje cells, is necessary to achieve the normal pattern of foliation and layering of the cerebellar cortex. Moreover, we discuss some of the functional tasks of cerebellar astrocytes and oligodendrocytes that are distinctive of cerebellar glia throughout the CNS. Notably, we report about the regulation of synaptic signalling in the molecular and granular layer mediated by Bergmann glia and parenchymal astrocytes, and the functional interaction between oligodendrocyte precursor cells and neurons. On the whole, this review provides an extensive overview of the available literature and some novel insights about the origin and differentiation of the variety of cerebellar glial cells and their function in the developing and mature cerebellum.

Keywords: AMPA; BG; Bergmann glia; EGL; FGF; GLAST; MN; NRG; Neuronal migration; Neuron–glial interactions; OPC; Oligodendrocytes; PTN; PTPζ; PWM; Purkinje cell synapses; RL; Radial glia; Scaffolding; VN; a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; external granular layer; fibroblast growth factor; glutamate/aspartate transporter; midkine; neuregulin; oligodendrocyte precursor cell; pleiotropin; prospective white matter; protein tyrosine phosphatase zeta; rhombic lip; ventricular neuroetiphelium.