PHYSIOLOGICAL AND BIOCHEMICAL-STUDIES ON THE CEREBELLAR CORTEX OF THE MURINE MUTANTS JOLTING AND MOTOR END-PLATE DISEASE

The activity of cerebellar Purkinje cells in the murine mutants "jolting" and "med" has been determined using extracellular electrical recordings in vivo and in isolated cerebellar slices. Most of the cells in the mutant brains failed to generate simple spontaneous action potentials, but they responded to climbing fibre inputs by generating complex potentials. The few mutant cells that were spontaneously active exhibited much lower firing frequencies than normal cells, and interval histograms of spontaneous activity were skewed towards longer intervals. The silent cells in mutant cerebellar slices could be activated by direct intracellular stimulation, by antidromic excitation and by the application of glutamate and high [K+]0. Activity was not restored by the application of bicuculline. It seems that the failure of the cerebellar Purkinje cells to generate simple spontaneous action potentials is not due to an inherent inexcitability of the soma or to the excessive activity of GABA-ergic inputs onto the cells. It is suggested that an abnormality in the behaviour of a Ca2+ channel is the most likely origin for the deficit in these mutant mice.