Role of Electrotonic Coupling in the Olivocerebellar System

The level of electrotonic coupling in the inferior olive is higher than in any other brain region. Connexin36 is the main protein that forms the olivary gap junctions. Yet, the functional role of electrotonic coupling in the cerebellar motor control remains to be determined. In this thesis mice that lack coupling among their olivary neurons were subjected to classical eyeblink conditioning. Cx36 deficient mice showed impaired learning-dependent timing in that they were not able to fix the timing of their conditioned responses at the moment when the unconditioned stimulus is about to occur. The timing of spike activities generated in the olive of coupling- deficient mice was abnormal in that their latencies in response to the unconditioned stimulus were inconsistent and that their overall synchrony was reduced. Whole cell recordings of olivary neurons in vivo showed that these different spiking activities over time result in part from altered interaction! s with their subthreshold oscillations. These results, combined with analysis of olivary activities in a computer simulation of the cerebellar system, suggest that electrotonic coupling among olivary neurons is necessary for proper synchronous oscillations in the inferior olive, which in turn determine the pace of the olivary responses necessary for learning-dependent timing in cerebellar motor control.

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