Ataxias and cerebellar dysfunction: involvement of synaptic plasticity deficits?

Adaptive processes within cerebellar circuits, such as long-term depression and long-term potentiation at parallel fiber-Purkinje cell synapses, have long been seen as important to cerebellar motor learning, and yet little attention has been given to any possible significance of these processes for cerebellar dysfunction and disease. Several forms of ataxia are caused by mutations in genes encoding for ion channels located at key junctures in pathways that lead to the induction of synaptic plasticity, suggesting that there might be an association between deficits in plasticity and the ataxic phenotype. Herein we explore this possibility and examine the available evidence linking the two together, highlighting specifically the role of P/Q-type calcium channels and their downstream effector small-conductance calcium-sensitive (SK2) potassium channels in the regulation of synaptic gain and intrinsic excitability, and reviewing their connections to ataxia.