Modification of saccadic eye movements by GABA-related substances. II. Effects of muscimol in monkey substantia nigra pars reticulata.

Abstract

The preceding study (21) showed that a gamma-aminobutyric acid (GABA) agonist or antagonist injected into the superior colliculus (SC) disrupted saccadic eye movements. The purpose of the present experiments was to determine whether this result was due to altering the inhibitory input to the SC from the substantia nigra pars reticulata (SNr). SNr cells are themselves inhibited by GABA. Injection of muscimol, a GABA agonist, into the SNr should increase the inhibition acting on SNr cells and should reduce the inhibition acting on the SC. If the effects of GABA inhibition in the SC results from terminals originating in the SNr, muscimol in the SNr should act like bicuculline in the SC. Muscimol in the SNr has the same general effect as bicuculline in the SC. The monkey made irrepressible saccades toward the contralateral visual field where cells in the SNr at the injection site had their visual or movement field. During visual fixation saccadic jerks occurred, interspersed with spontaneous saccades, instead of saccades to visual targets or to remembered targets. Saccades to remembered targets were more vulnerable to these saccadic intrusions than were saccades to visual targets. Since muscimol in the SNr acts like bicuculline in the SC, we conclude that a substantial fraction of GABA-mediated inhibitory inputs in the SC originates from the SNr. These experiments, in conjunction with previous experiments, show that the SNr exerts a tonic inhibition on saccade-related cells in SC and that this inhibition is mediated by GABA. The role of the SNr in initiation of saccades to remembered targets is particularly important since these saccades are more severely disrupted by muscimol in the SNr as well as in the SC. We suggest that both of these conclusions about eye movement might apply to skeletal movements as well. First, the basal ganglia contribute to the initiation of movement by a release of the target structure from tonic inhibition. Second, this mechanism is particularly critical of the movements based on stored or remembered signals that are not currently available as incoming sensory inputs.