EFFECTS OF BOTULINUM NEUROTOXIN TYPE-A ON ABDUCENS MOTONEURONS IN THECAT - ALTERATIONS OF THE DISCHARGE PATTERN

The discharge characteristics that abducens motoneurons exhibit after paralysis of the lateral rectus muscle with botulinum neurotoxin type A were studied in the alert cat. Antidromically identified motoneurons were recorded during both spontaneous and vestibularly induced eye mo vements. A single injection of 0.3 ng/kg produced a complete paralysis of the lateral rectus muscle lasting for about 12-15 days, whereas af ter 3 ng/kg the paralysis was still complete at the longest time check ed, three months. Motoneurons recorded under the effect of the low dos e showed differences in their sensitivities to both eye position and v elocity according to the direction of the previous and ongoing movemen ts, respectively. These directional differences could be explained by post-saccadic adaptation of the non-injected eye in the appropriate di rection for reducing ocular misalignment. Thus, backward and forward p ost-saccadic drifts accompanied on-and off-directed saccades, respecti vely. The magnitude of the drift was similar to the magnitude of chang es in eye position sensitivity. The discharge of the high-dose-treated motoneurons could be described in a three-stage sequence. During the initial 10-12 days, motoneuronal discharge resembled the effects of ax otomy, particularly in the loss of tonic signals and the presence of e xponential-like decay of firing after saccades. In this stage, the con duction velocity of abducens motoneurons was reduced by 21.4%. The sec ond stage was characterized by an overall reduction in firing rate tow ards a tonic firing al 15-70 spikes/s. Motoneurons remained almost unm odulated for all types of eye movement and thus eye position and veloc ity sensitivities were significantly reduced. Tonic firing ceased only when the animal became drowsy, but was restored by alerting stimuli. In addition, the inhibition of firing for off-directed saccades was mo re affected than the burst excitation during on-directed saccades, sin ce in many cells pauses were almost negligible. These alterations coul d not be explained by adaptational changes in the movement of the non- injected eye. Finally, after 60 days the initial stages of recovery we re observed. The present results indicate that the high dose of botuli num neurotoxin produces effects on the motoneuron not attributable to the functional disconnection alone, but to a direct effect of the neur otoxin in the motoneuron and/or its synaptic inputs. (C) 1997 IBRO. Pu blished by Elsevier Science Ltd.