A computational model of homeostatic cerebellar compensation of ageing in vestibulo-ocular reflex adaptation

Abstract

The vestibulo-ocular reflex (VOR) stabilises vision during head motion. Age-related structural changes predict a linear VOR decay, whereas epidemiological data show a non-linear temporal profile. Here, we model cerebellar-dependent VOR adaptation to link structural and functional changes throughout ageing. We posit that three neurosynaptic factors codetermine VOR ageing patterns: electrical coupling between inferior olive neurons, intrinsic plasticity at Purkinje cell synapses, and long-term spike timing dependent plasticity at parallel fibre - Purkinje cell synapses as well as mossy fibre - medial vestibular nuclei synapses. Our cross-sectional simulations show that long-term plasticity acts as a global homeostatic mechanism mediating the non-linear temporal profile of VOR. Our results also suggest that intrinsic plasticity at Purkinje cells acts as a local homeostatic mechanism sustaining VOR at old ages. Importantly, longitudinal simulations show that residual fibres coding for the peak and trough of the VOR cycle constitute a predictive hallmark of VOR ageing trajectories.