Survival strategies for mouse cerebellar Purkinje neurons lacking PMCA2

Expression of the fast calcium extrusion protein, PMCA2, in the cerebellum is amongst the highest found throughout the central nervous system, and unsurprisingly PMCA2 knockout mice exhibit cerebellar ataxia or loss of controlled movement. The sole output neurons of the cerebellar cortex, Purkinje neurons, are functionally compromised in these knockout mice, yet remarkably these neurons survive. In this mini-review we review and speculate on the importance of multiple PMCA2 dependent actions at cellular and synaptic sites within the cerebellar Purkinje neuron network. We also explore how loss of PMCA2−/− can lead to the ataxic phenotype, but can paradoxically also minimise calcium rises in cerebellar Purkinje neurons, thereby ensuring their resilience and survival.