Cerebellar control of eye movements studied with injection of harmaline in the trained baboon

1. The alteration of the cortical cerebellar mechanisms resulting from the activation of the olivo-cerebellar pathway by Harmaline (H) administered at doses which were subthreshold for skeletomotor tremor (5 mg/kg, IM) yields, in the trained Baboon (Papio papio), a marked decrease of oculomotor system performance. 2. The mean angular excursion of the spontaneous eye movements produced in the dark over a given period of time is increased by 50%. The increase is basically due to an increase of the number of saccades in the 0-20 degrees amplitude range. 3. The eye movements in response to a slow target displacement are altered as evidenced by a decrease of the smooth pursuit gain, a 60% increase in latency, and by intrusive saccades. The effects are dose dependent so that around 8 mg/kg of H, smooth pursuit is totally suppressed. 4. The saccadic system is also altered, Stepping target tracking shows dysmetria and increase of the amplitude of the fixation eye movements. The velocity-amplitude relationship of the saccades is not modified but the saccadic reaction time is increased by 50%. The observed alterations are in no way similar to the tremor commonly induced by the drug, at skeletal level. In fact, no ocular tremor at 8 to 10 Hz was recorded. 5. In conclusion, administration of H alters considerably the control and the stability of the oculomotor system in a way similar to that resulting from partial or total cerebellectomy. It may thus be possible to use the drug to simulate, in a reversible manner, cerebellar dysfunctions and study the involvement of the cerebellum in oculomotor control.