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 Ϯ 0.3, n ϭ 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. 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 Ca 2ϩ -activated K ϩ ) 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. Significance Statement I have previously studied the "non-synaptic" plasticity of the intrinsic excitability in the cerebellar Purkinje cells (Belmeguenai et

Synergistic excitability plasticity in cerebellar functioning

“…Additionally, recent studies on the heterogeneous excitability among PC dendritic branches suggest that the underlying mechanisms are associated with BK, SK, and A-type K + channels [45,125,[143][144][145], arguing against a uniform pattern of intrinsic excitability. Taken together, it is important to consider that PC dendritic excitability may be heterogeneous [45,127,135,145] (Fig. 3A).…”

“…Several studies have sought to address the question of how PC IP regulates nuclear activity and motor performance [44,45,125,127,159]. At present, it is difficult to believe that a single form of plasticity is dominant in learning processes, as previously hypothesized [15].…”

“…Pf-synaptic activity which induces Pf-LTP also enhances the dendrite excitability and facilitates an influx of Ca 2+ at spine and shaft [44,45] and thus modulates the direction of LTP/LTD induction. The excitable dendritic arbors may prompt the contrast of synaptic responsiveness via synaptic plasticity within their branch field and heterogeneous excitability which influences the electroconductivity of postsynaptic potential [127] (see Fig. 3).…”

“…Pf-synaptic activity that induces Pf-LTP also enhances the dendrite excitability and facilitates Ca 2+ influx [44,45]. The highly excitable dendritic arbors enhance the contrast of synaptic responsiveness via both synaptic plasticity within the branch field and heterogeneous excitability [127]. Therefore, sensory-afferent activity enlarges the receptive field through Pf-LTP/IP, which may enhance the contrast among the spatio-temporal Pf inputs in the conductive dendrites or may facilitate the discrimination of Cf-co-activated Pf signals (Fig.…”

“…Further, comparing the thickness of the molecular layer of the cerebellum and the length of PC dendrite arbors, there might be distinct differences in the electroconductivity in the PC dendrites between species (e.g., rodents vs. carnivores vs. primates, depending on the size of cerebellum or the thickness of the molecular layer). It is because the compartmentalization of the dendritic branches in rat PCs necessitates the separation of more than 80 lm [127]. Larger dendrites might contain more regions that are locally excitable.…”