Cerebellar Development and Circuit Maturation: A Common Framework for Spinocerebellar Ataxias

Front Neurosci. 2020 Apr 2;14:293. doi: 10.3389/fnins.2020.00293. eCollection 2020.

Abstract

Spinocerebellar ataxias (SCAs) affect the cerebellum and its afferent and efferent systems that degenerate during disease progression. In the cerebellum, Purkinje cells (PCs) are the most vulnerable and their prominent loss in the late phase of the pathology is the main characteristic of these neurodegenerative diseases. Despite the constant advancement in the discovery of affected molecules and cellular pathways, a comprehensive description of the events leading to the development of motor impairment and degeneration is still lacking. However, in the last years the possible causal role for altered cerebellar development and neuronal circuit wiring in SCAs has been emerging. Not only wiring and synaptic transmission deficits are a common trait of SCAs, but also preventing the expression of the mutant protein during cerebellar development seems to exert a protective role. By discussing this tight relationship between cerebellar development and SCAs, in this review, we aim to highlight the importance of cerebellar circuitry for the investigation of SCAs.

Keywords: Purkinje cell degeneration; cerebellar circuits; cerebellum; circuit maturation; spinocerebellar ataxia.

Publication types

  • Review