Synergistic excitability plasticity in cerebellar functioning

Abstract

The cerebellum, a universal processor for sensory acquisition and internal models, and its association with synaptic and nonsynaptic plasticity have been envisioned as the biological correlates of learning, perception, and even thought. Indeed, the cerebellum is no longer considered merely as the locus of motor coordination and its learning. Here, we introduce the mechanisms underlying the induction of multiple types of plasticity in cerebellar circuit and give an overview focusing on the plasticity of nonsynaptic intrinsic excitability. The discovery of long-term potentiation of synaptic responsiveness in hippocampal neurons led investigations into changes of their intrinsic excitability. This activity-dependent potentiation of neuronal excitability is distinct from that of synaptic efficacy. Systematic examination of excitability plasticity has indicated that the modulation of various types of Ca²⁺ - and voltage-dependent K⁺ channels underlies the phenomenon, which is also triggered by immune activity. Intrinsic plasticity is expressed specifically on dendrites and modifies the integrative processing and filtering effect. In Purkinje cells, modulation of the discordance of synaptic current on soma and dendrite suggested a novel type of cellular learning mechanism. This property enables a plausible synergy between synaptic efficacy and intrinsic excitability, by amplifying electrical conductivity and influencing the polarity of bidirectional synaptic plasticity. Furthermore, the induction of intrinsic plasticity in the cerebellum correlates with motor performance and cognitive processes, through functional connections from the cerebellar nuclei to neocortex and associated regions: for example, thalamus and midbrain. Taken together, recent advances in neuroscience have begun to shed light on the complex functioning of nonsynaptic excitability and the synergy.

Keywords: Purkinje cells; cerebellar efferent projections; cerebellar higher-order functions; cerebellum; dendritic excitability; intrinsic plasticity; synaptic plasticity; synergy mechanisms of multiple plasticity.