Besides Purkinje cells and granule neurons: an appraisal of the cell biology of the interneurons of the cerebellar cortex

Abstract

Ever since the groundbreaking work of Ramon y Cajal, the cerebellar cortex has been recognized as one of the most regularly structured and wired parts of the brain formed by a rather limited set of distinct cells. Its rather protracted course of development, which persists well into postnatal life, the availability of multiple natural mutants, and, more recently, the availability of distinct molecular genetic tools to identify and manipulate discrete cell types have suggested the cerebellar cortex as an excellent model to understand the formation and working of the central nervous system. However, the formulation of a unifying model of cerebellar function has so far proven to be a most cantankerous problem, not least because our understanding of the internal cerebellar cortical circuitry is clearly spotty. Recent research has highlighted the fact that cerebellar cortical interneurons are a quite more diverse and heterogeneous class of cells than generally appreciated, and have provided novel insights into the mechanisms that underpin the development and histogenetic integration of these cells. Here, we provide a short overview of cerebellar cortical interneuron diversity, and we summarize some recent results that are hoped to provide a primer on current understanding of cerebellar biology.

Laminar Fate and Phenotype Specification of Cerebellar GABAergic Interneurons

“…Rather, it is likely that exit from the cell cycle defines a generic GABAergic interneuron identity, marks the onset of differentiation, and makes the cell competent to choose its specific phenotype in response to extrinsic cues. However, the observation that postmitotic interneurons maintain the expression of mitotic markers, such as Ki67 , suggests that they do not enter a full-blown G 0 , but persist in an intermediate state required to complete specification (Schilling et al, 2008).…”

Sonic hedgehog patterning during cerebellar development

“…This effect was significant both at 1 and 2 days in vitro, whereas it did not occur in presence of the Shh-antagonist cyclopamine [137]. In addition, Shh mitogenic effect on newborn Pax-2 + cells disappears at late postnatal stages as P7, when the bulk of GABAergic interneurons have been already produced [125,138]. Gene expression analysis of sorted GFP + cells from Pax-2-GFP transgenic mice revealed that Shh pathway is active in immature Pax-2 + interneurons, which express both the Shh receptor Ptch1 and the Shh target gene Gli1 [137].…”

Ablation of Retinal Horizontal Cells from Adult Mice Leads to Rod Degeneration and Remodeling in the Outer Retina

“…While projection neurons, e.g., pyramidal cells, comprise a rather homogeneous group of neurons with relatively uniform features (Flames and Marín, 2005), interneurons show an enormous structural and functional diversity in the brain, including the retina (Masland, 2001;Schilling et al, 2008). They represent important elements of neuronal networks as they are often inhibitory and balance excitation (Markram et al, 2004;Moore et al, 2010).…”