Role of electrical synapses in multidimensional population activity of Golgi cell network in cerebellar cortex

Abstract

Inhibitory neuronal network of Golgi cells (GoCs) connected with gap junctions (GJs) in cerebellum display multiple modes during spontaneous behaviour. A network-wide modulation of GoC activity that occurs at a slow pace is correlated with the level of whisking and locomotion. On the other hand, a faster population activity that arises from heterogeneous GoC responses mixed in space is responsible for encoding more precise information. By constructing a biologically detailed circuit model of GoC, it was possible to reproduce the observed common population mode and the distributed modes. However, these properties were no longer present when electrical coupling was eliminated. The strength and variability of electrical synaptic connections between GABAergic interneurons play a crucial role in determining spike synchrony within neuronal networks. The electrical transmission of spike afterhyperpolarization serves as a critical factor in enabling oscillatory population synchronization, allowing rhythmic firing to occur even in the presence of significant heterogeneities. However, the mechanism behind the multidimensional population activity of GoCs still remains unclear. To this end, we simulated physiologically realistic and morphologically reduced models of GoCs connected with GJs. We used MPMOSS, a stochastic search algorithm, to generate 40-parameter randomized models spanning 14 active and passive ion channels biophysically constraint by their localization profiles and gating kinetic to search for valid cerebellar GoC models. The models that fell in the range of 14 sub- and supra- threshold cellular-scale electrophysiological measurements of cerebellar GoCs of rats were considered as valid models. We got 486 valid models out of 50,000 generated models that were electrophysiologically valid, manifested heterogeneity, as their biological counterparts, and were widespread throughout the parametric space thus displaying degeneracy. We then connected valid GoCs with GJs to characterize the two cell-network. Our results show that low pass filtering of signal, due to the RC circuit, as it traverses GJs and its resonance at low frequency could be the responsible for the manifestation of multidimensional population activity of GoCs. Low pass filtering creates a virtual compartment that can confine distinct activity within a subset of GoCs and resonance at low frequency may allow network-wide synchronization of GoC activity.