Climbing Fiber Burst Size and Olivary Sub-threshold Oscillations in a Network Setting

Abstract

The inferior olivary nucleus provides one of the two main inputs to the cerebellum: the so-called climbing fibers. Activation of climbing fibers is generally believed to be related to timing of motor commands and/or motor learning. Climbing fiber spikes lead to large all-or-none action potentials in cerebellar Purkinje cells, overriding any other ongoing activity and silencing these cells for a brief period of time afterwards. Empirical evidence shows that the climbing fiber can transmit a short burst of spikes as a result of an olivary cell somatic spike, potentially increasing the information being transferred to the cerebellum per climbing fiber activation. Previously reported results from in vitro studies suggested that the information encoded in the climbing fiber burst is related to the occurrence of the spike relative to the ongoing sub-threshold membrane potential oscillation of the olivary cell, i.e. that the phase of the oscillation is reflected in the size of the climbing fiber burst. We used a detailed three-compartmental model of an inferior olivary cell to further investigate the possible factors determining the size of the climbing fiber burst. Our findings suggest that the phase-dependency of the burst size is present but limited and that charge flow between soma and dendrite is a major determinant of the climbing fiber burst. From our findings it follows that phenomena such as cell ensemble synchrony can have a big effect on the climbing fiber burst size through dendrodendritic gap-junctional coupling between olivary cells. The inferior olive is a nucleus in the brain stem with neurons that exhibit continuous sub-threshold activity and are electrically coupled by gap junctions. It is implicated in execution and learning of motor skills and it is often assumed that it provides a teacher signal to the cerebellum. Models based on this theory generally require a continuously updated quantitative value to be sent to the cerebellum, yet the inferior olive fires spikes at a low rate of approximately 1 Hz, making reconciliation of model and biological system problematic. However, it has also been shown that olivary cells can generate an axonal burst of spikes for every somatically recorded action potential, theoretically rendering them capable of transmitting more information per event. Using a detailed neuronal model of an inferior olive cell, we examined what factors may underlie the axonal burst size. We found that leak currents between dendrite and soma and electrically coupled dendrites are major determinants. From our findings and current literature it follows that the inferior olive may be capable of adapting the speed at which motor tasks in the cerebellum are learned, depending on the synchrony of sub-threshold activity in clusters of electrically coupled cells.