Modification of Synaptic-Input Clustering by Intrinsic Excitability Plasticity on Cerebellar Purkinje Cell Dendrites

Abstract

The role of dendrites in the integration of widespread synaptic activity has been studied in experiments and theories (Johnston et al., 1996; Magee, 2007). However, whether the conduction of synaptic currents from dendrites to the soma depends on excitability of those dendritic branches is unclear. How modulation of the branch excitability affects the conduction of synaptic inputs and their selection on dendrites is also elusive. Here, I performed simultaneous voltage-clamp recordings from the soma and dendrites of single cerebellar Purkinje neurons in male Sprague-Dawley rats and analyzed the relationship between spontaneous EPSCs on both sides. I found that EPSCs on distal dendrites have a salient discordance in amplitude compared with those on the soma. Furthermore, individual ratios of the EPSC concurrently recorded on the soma and dendrites were not unique, but discrete, suggesting the occurrence of various attenuations in different paths of dendritic branches to the soma. The obtained data and simulations indicate several distinct groups (4.5 ± 0.3, n = 22 somatodendritic recordings) of co-occurred synaptic inputs in Purkinje cell dendrites. This clustering of synaptic currents was suggested to emerge at farther distances than the secondary bifurcations. Finally, ratios of the co-EPSCs were uniformly distributed after either intrinsic plasticity induction or SK-channel blockade. Overall, results suggest that in Purkinje cells the excitability along the dendrite processes modulates the conduction of EPSCs and makes active inputs heterogeneous through SK channel activity, intrinsic plasticity, and dendritic branching. These properties of dendrites may confer branch-specific computational power to neurons.SIGNIFICANCE STATEMENT I have previously studied the "non-synaptic" plasticity of the intrinsic excitability in the cerebellar Purkinje cells (Belmeguenai et al., 2010), and branch-specific increase of intrinsic excitability of the dendrites (Ohtsuki et al., 2012b; Ohtsuki and Hansel, 2018) through the downregulation of SK (small conductance Ca²⁺-activated K⁺) channels. In this study, I show that a dendritic filtering of synaptic electroconductivity is heterogeneous among the branches on distal dendrites and that the increase in the dendritic excitability accompanied with the intrinsic plasticity alters a state with the heterogeneity to a globally excitable state in Purkinje neurons. My findings propose a new learning model relying on the intrinsic excitability plasticity of the dendritic branch fields.

Keywords: SK channels; branch-specific clustering; cerebellar Purkinje cells; dendrites; intrinsic plasticity; synaptic currents.