SUMMARY1. Spontaneous discharges and evoked responses of Purkinje cells have been studied in the anterior lobe vermis of the cerebellum in cats anaesthetized with thiopentone sodium.2. Spontaneous activitywas oftwo kinds: (a) single spikes which occurred in long trains and were discharged at average frequencies of 50-125/sec and (b) burst responses due to climbing fibre (CF) activation of the cell. These occurred at an average frequency close to 1/sec.3. CF responses were evoked by either stimulation of the Afl fibres of the superficial radial nerve (SRN) or by an electrode inserted into the deep white matter near the fastigial nucleus (JF electrode).4. A suppression of the discharge of single spikes was frequently observed to follow a CF response, whether it occurred naturally or was produced by a stimulus. These pauses in spontaneous discharge (post-CF pause) lasted for approximately 100 msec, but they did not have a one-toone relationship with the CF responses. Occasionally a pause in the spontaneous activity was elicited by stimuli that failed to evoke the cell.5. For a period following a peripheral stimulus, a Purkinje cell could not be further excited by a second peripheral stimulus (interaction). JF stimulation could still excite the cell. Evidence was obtained that there was no significant inhibition during the period of depressed excitability to peripheral stimulation.6. The control over the input of activity to the cerebellum through the CF system appears to be imposed at an extra-cerebellar site. The olivary nuscles was suggested as a strong possibility.7. Some possible mechanisms responsible for the post-CF pause were discussed. Disfacilitation of Purkinje cells by suppression of granule cell discharges seems to give the best fit to the data.

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The effects of phenytoin (PHT) on the spontaneous activity of cerebellar Purkinje cells and the drug serum levels have been examined following both intravenous and intraperitoneal administration in rats. Purkinje cell activity was assessed by on-line computer analysis of interspike interval distributions. PHT levels were assayed in blood samples taken at the end of the electrophysiological experiments and in successive samples obtained in parallel experiments over periods corresponding to when electrophysiological recordings were made. Single intravenous doses of PHT (10 mg/kg) produced a decrease in the discharge rate in individual Purkinje cells with a time course which was delayed and prolonged compared with the changes in serum levels of PHT. A single intraperitoneal dose of PHt (100 mg/kg) produced a statistically significant (p < 0.02) decrease in Purkinje cell discharge rate. Similar results (p < 0.01) were obtained after pretreatment with PHT (50 mg/kg daily for 14 days, including the day of the experiment). Both injection schedules produced nontoxic serum PHT levels during the recording period. Pretreatment with PHT doses of 10 mg/kg for 14 days (including the experimental day) produced a smaller decrease in Purkinje cell discharge rate (p < 0.05). When pretreatment ceased the day before the electrophysiological experiment, no significant changes in Purkinje cell activity were observed, and serum PHT levels were not detectable at the end of the experiment. None of the pretreatment schedules produced overt signs of cerebellar dysfunction or motor impairment. These findings indicate that PHT may increase the output from the cerebellum by suppressing Purkinje cell activity. Since this effect occurs without producing cerebellar symptoms, it may account for some of the therapeutic action of PHT at nontoxic levels in man.

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