Role of Myelination in the Development of a Uniform Olivocerebellar Conduction Time

Abstract

Lang, Eric J. and Jack Rosenbluth. Role of myelination in the development of a uniform olivocerebellar conduction time. J Neurophysiol 89: 2259 -2270, 2003. First published December 18, 2002 10.1152/jn.00922.2002. Purkinje cells generate simultaneous complex spikes as a result of olivocerebellar activity. This synchronization (to within 1 ms) is thought to result from electrotonic coupling of inferior olivary neurons. However, the distance from the inferior olive (IO) varies across the cerebellar cortex. Thus signals generated simultaneously at the IO should arrive asynchronously across the cerebellar cortex, unless the length differences are compensated for. Previously, it was shown that the conduction time from the IO to the cerebellar cortex remains nearly constant at Ϸ4 ms in the rat, implying the existence of such compensatory mechanisms. Here, we examined the role of myelination in generating a constant olivocerebellar conduction time by investigating the latency of complex spikes evoked by IO stimulation during development in normal rats and myelin-deficient mutants. In normal rats, myelination not only reduced overall olivocerebellar conduction time, but also disproportionately reduced the conduction time to vermal lobules, which had the longest response latencies prior to myelination. The net result was a nearly uniform conduction time. In contrast, in myelin-deficient rats, conduction time differences to different parts of the cerebellum remained during the same developmental period. Thus myelination is the primary factor in generating a uniform olivocerebellar conduction time. To test the importance of a uniform conduction time for generating synchronous complex spike activity, multiple electrode recordings were obtained from normal and myelin-deficient rats. Average synchrony levels were higher in normal rats than mutants. Thus the uniform conduction time achieved through myelination of olivocerebellar fibers appears to be essential for the normal expression of complex spike synchrony. I N T R O D U C T I O NInferior olivary (IO) neurons are electrotonically coupled via numerous gap junctions (Llinás and Yarom 1981;Llinás et al. 1974;Sotelo et al. 1974). Indeed, the density of neuronal gap junctions appears to be higher in the IO than in any other CNS region (Belluardo et al. 2000;Condorelli et al. 1998;De Zeeuw et al. 1995). This coupling allows IO neurons to generate precisely (on a millisecond time scale) synchronized activity that results in simultaneous complex spike (CS) activity in the cerebellum (Lang et al. 1999;Sasaki et al. 1989;Sugihara et al. 1993;Yamamoto et al. 2001).Maintenance of the synchronization present in IO discharges presents a challenge for the olivocerebellar system because the length of the olivocerebellar pathway to different points on the cerebellar cortex varies. In rats, there can be more than a twofold difference in the length of the olivocerebellar projection to different regions of the cortex (Sugihara et al. 1993). To preserve the precise synchronization present at...

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