Nystagmus induced by pharmacological inactivation of the brainstem ocular motor integrator in monkey

A common cause of pathological nystagmus is malfunction of the mechanism by which the brain integrates eye velocity signals to produce eye position co mmands. For horizontal gaze, neurons in the nucleus prepositus hypoglossi-m edial vestibular nucleus region (NPH-MVN) play a vital role in this neural integrator function. We studied the effects on gaze stability of pharmacolo gical intervention in the NPH-MVN of monkeys by microinjections of eight dr ugs. Agents with agonist or antagonist actions at gamma-aminobutyric acid ( GABA), glutamate, and kainate receptors all caused gaze-evoked nystagmus wi th centripetal eye drifts; glycine and strychnine had no effect. When the G ABA(A)-agonist muscimol was injected near the center of MVN, the eyes drift ed away from the central position with increasing-velocity waveforms, imply ing an unstable neural integrator. The observed effects of these drugs on g aze stability may be related to inactivation either of neurons within NPH-M VN or the cerebellar projections to them that control the fidelity of neura l integration. Drugs that influence GABA or glutamine transmission may have a role in the treatment of nystagmus due to an abnormal neural integrator. Published by Elsevier Science Ltd.