Voltage- and Branch-Specific Climbing Fiber Responses in Purkinje Cells

Abstract

Summary: Climbing fibers (CFs) provide instructive signals driving cerebellar learning, but mechanisms causing the variable CF responses in Purkinje cells (PCs) are not fully understood. Using a new experimentally validated PC model, we unveil the ionic mechanisms underlying CF-evoked distinct spike waveforms on different parts of the PC. We demonstrate that voltage can gate both the amplitude and the spatial range of CF-evoked Ca2+ influx by the availability of K+ currents. This makes the energy consumed during a complex spike (CS) also voltage dependent. PC dendrites exhibit inhomogeneous excitability with individual branches as computational units for CF input. The variability of somatic CSs can be explained by voltage state, CF activation phase, and instantaneous CF firing rate. Concurrent clustered synaptic inputs affect CSs by modulating dendritic responses in a spatially precise way. The voltage- and branch-specific CF responses can increase dendritic computational capacity and enable PCs to actively integrate CF signals. : Zang et al. find that the availability of K+ currents regulates Ca2+ influx and corresponding energy consumption during climbing fiber input in Purkinje cell dendrites. They systematically explore the mechanisms underlying variable somatic complex spikes and identify branchlet-specific computation in dendrites. Keywords: cerebellum, Purkinje cell, climbing fiber, complex spikes, dendritic spikes, dendritic excitability, biophysical model, energy consumption