The role of olivary phase-locking oscillations in cerebellar sensorimotor adaptation

Abstract

AbstractThe function of the olivary nucleus is key to cerebellar adaptation as it modulates long term synaptic plasticity between parallel fibres and Purkinje cells. Here, we posit that the neural dynamics of the inferior olive (IO) network, and in particular the phase of subthreshold oscillations with respect to afferent excitatory inputs, plays a role in cerebellar sensorimotor adaptation. To test this hypothesis, we first modelled a network of 200 multi-compartment Hodgkin-Huxley IO cells, electrically coupled via anisotropic gap junctions. The model IO neural dynamics captured the properties of real olivary activity in terms of subthreshold oscillations and spike burst responses to dendritic input currents. Then, we integrated the IO network into a large-scale olivo-cerebellar model to study vestibular ocular reflex (VOR) adaptation. VOR produces eye movements contralateral to head motion to stabilise the image on the retina. Hence, studying cerebellar-dependent VOR adaptation provided insights into the functional interplay between olivary subthreshold oscillations and responses to retinal slips (i.e., image movements triggering optokinetic adaptation). Our results showed that the phase-locking of IO subthreshold oscillations to retina slip signals is a necessary condition for cerebellar VOR learning. We also found that phase-locking makes the transmission of IO spike bursts to Purkinje cells more informative with respect to the variable amplitude of retina slip errors. Finally, our results showed that the joint action of IO phase-locking and cerebellar nuclei GABAergic modulation of IO cells’ electrical coupling is crucial to increase the state variability of the IO network, which significantly improves cerebellar adaptation.Author summaryThis study aims to elucidate the dual functionality of the inferior olive (IO) in cerebellar motor control, reconciling hypotheses regarding its role as either a timing or instructive signal. Specifically, we explore the role of subthreshold oscillations (STOs) within the IO, investigating their potential influence on the climbing fibres-to-Purkinje cell spike pattern responses and subsequent cerebellar adaptation, notably during the vestibulo ocular reflex. Aiming these objectives, we constructed a detailed olivary network model within a cerebellar neural network, enabling a mechanistic analysis of the functional relevance of STOs in spike burst generation, propagation, and modulation within target Purkinje cells. Our findings reveal the intricate nature of complex spike bursts triggered by climbing fibres—IO axons—into Purkinje cell dendrites, demonstrating a hybrid nature involving binary clock-like signals and graded spikelet components acting as an instructive signal.