Many neurons that regulate motor coordination, including Purkinje cells and their cerebellar nuclear targets, spontaneously fire tens of action potentials per second. Such high intrinsic activity raises questions regarding how spikes are generated, how synaptic strength is maintained, and how synaptic plasticity occurs. Through electrophysiology, computer simulations, and ultrastructural studies, we find, first, that rapid firing by Purkinje neurons requires a tetrodotoxin-sensitive "resurgent" Na current, resulting from open-channel block of Na channels. Second, Purkinje neurons signal via an effective spillover-mediated transmission. Third, long-term potentiation of cerebellar nuclear EPSCs is independent of postsynaptic spiking and appears optimized to detect coincident synaptic excitation and inhibition.

08/08/07