Spike burst-pause dynamics of Purkinje cells regulate sensorimotor adaptation.

Niceto R Luque,Francisco Naveros,Eduardo Ros,Angelo Arleo,Richard R Carrillo,Francesco P Battaglia

doi:10.1371/journal.pcbi.1006298

Abstract

Cerebellar Purkinje cells mediate accurate eye movement coordination. However, it remains unclear how oculomotor adaptation depends on the interplay between the characteristic Purkinje cell response patterns, namely tonic, bursting, and spike pauses. Here, a spiking cerebellar model assesses the role of Purkinje cell firing patterns in vestibular ocular reflex (VOR) adaptation. The model captures the cerebellar microcircuit properties and it incorporates spike-based synaptic plasticity at multiple cerebellar sites. A detailed Purkinje cell model reproduces the three spike-firing patterns that are shown to regulate the cerebellar output. Our results suggest that pauses following Purkinje complex spikes (bursts) encode transient disinhibition of target medial vestibular nuclei, critically gating the vestibular signals conveyed by mossy fibres. This gating mechanism accounts for early and coarse VOR acquisition, prior to the late reflex consolidation. In addition, properly timed and sized Purkinje cell bursts allow the ratio between long-term depression and potentiation (LTD/LTP) to be finely shaped at mossy fibre-medial vestibular nuclei synapses, which optimises VOR consolidation. Tonic Purkinje cell firing maintains the consolidated VOR through time. Importantly, pauses are crucial to facilitate VOR phase-reversal learning, by reshaping previously learnt synaptic weight distributions. Altogether, these results predict that Purkinje spike burst-pause dynamics are instrumental to VOR learning and reversal adaptation.

Highlights

The cerebellum controls fine motor coordination including online adjustments of eye movements [1]
Cerebellar Purkinje cells regulate accurate eye movement coordination. It remains unclear how cerebellar-dependent oculomotor adaptation depends on the interplay between Purkinje cell characteristic response patterns: tonic, high frequency bursting, and post-complex spike pauses
We explore the role of Purkinje spike burst-pause dynamics in vestibular ocular reflex (VOR) adaptation

Summary

Introduction

The cerebellum controls fine motor coordination including online adjustments of eye movements [1]. The inhibitory projections of Purkinje cells to medial vestibular nuclei (MVN) mediate the acquisition of accurate oculomotor control [2, 3]. We consider the role of cerebellar Purkinje cells in the adaptation of the vestibular ocular reflex (VOR), which generates rapid contralateral eye movements that maintain images in the fovea during head rotations (Fig 1A). The VOR is mediated by the three-neuron reflex arc comprised of connections from the vestibular organ via the medial vestibular nuclei (MVN) to the eye motor neurons[3,4,5]. VOR control is purely feedforward [6] and it relies on several cerebellar-dependent adaptive mechanisms driven by sensory errors (Fig 1C). Very few studies have focused on the relation between the characteristics spike response patterns of Purkinje cells and VOR adaptation, which is the main focus of this study

Methods

Results

Discussion

Conclusion