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 commands. For horizontal gaze, neurons in the nucleus prepositus hypoglossi-medial vestibular nucleus region (NPH-MVN) play a vital role in this neural integrator function. We studied the effects on gaze stability of pharmacological intervention in the NPH-MVN of monkeys by microinjections of eight drugs. Agents with agonist or antagonist actions at gamma-aminobutyric acid (GABA), glutamate, and kainate receptors all caused gaze-evoked nystagmus with centripetal eye drifts; glycine and strychnine had no effect. When the GABAA-agonist muscimol was injected near the center of MVN, the eyes drifted away from the central position with increasing-velocity waveforms, implying an unstable neural integrator. The observed effects of these drugs on gaze stability may be related to inactivation either of neurons within NPH-MVN or the cerebellar projections to them that control the fidelity of neural integration. Drugs that influence GABA or glutamine transmission may have a role in the treatment of nystagmus due to an abnormal neural integrator.
Arnold
D B
DB
Department of Ophthalmology and Biomedical Engineering, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Robinson
D A
DA
Leigh
R J
RJ
D000818:Animals; D001933:Brain Stem / Q000503:physiopathology*; D005133:Eye Movements / Q000187:drug effects; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005998:Glycine / Q000037:antagonists & inhibitors; D008253:Macaca mulatta; D018377:Neurotransmitter Agents / Q000502:physiology*; D009759:Nystagmus, Pathologic / Q000139:chemically induced / Q000503:physiopathology*; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018755:GABA Agonists; D018756:GABA Antagonists; D005998:Glycine; D018377:Neurotransmitter Agents; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate