Activity of pallidal neurons in the monkey during dyskinesia induced by injection of bicuculline in the external pallidum.

Abstract

The present study was undertaken to determine whether dyskinesia, resulting from injection of the GABA antagonist bicuculline into the external globus pallidus of intact monkeys, is induced by hyperactivity of local external pallidal neurons and ensuing hypoactivity of neurons in the internal globus pallidus, at the output of the basal ganglia. Accordingly, 86% of responding external pallidal neurons increased and 56% of internal pallidal neurons decreased their activity, either exclusively or within biphasic responses. Whereas 29% of external pallidal neurons decreased and as much as 85% of internal pallidal neurons increased their activity. The latter unpredicted responses may be explained by diffusion of bicuculline from the external to the internal pallidum and by lateral monosynaptic inhibition within the external and its mirror image in the internal pallidum. With respect to individual injection sites, the hypoactive neurons in the internal pallidum tended to be grouped together and surrounded by hyperactive or unresponsive neurons. The changes occurred before and persisted during dyskinesia, suggesting that they were required to induce and maintain the dyskinesia. There were also changes in firing patterns, comprising long periods of silence, especially in external pallidal neurons close to the injection site. The periods of silence did not appear to result from depolarization block but rather from activation of receptors of inhibitory neurotransmission other than type A GABA. Dyskinesia therefore does not appear to result exclusively from a simple imbalance of activity between the pallidal segments, with hyperactivity in the external and hypoactivity in the internal segment, but also from imbalances within each pallidal segment, possibly with a center-surround organization.