ROLE OF THE CAUDAL FASTIGIAL NUCLEUS IN SACCADE GENERATION .2. EFFECTS OF MUSCIMOL INACTIVATION

1. We studied the effect of temporarily inhibiting neurons in the caud al fastigial nucleus in two rhesus macaques trained to make saccades t o jumping targets. We placed injections of the gamma-aminobutyric acid (GABA) agonist muscimol unilaterally or bilaterally at sites in the c audal fastigial nucleus where we had recorded saccade-related neurons a few minutes earlier. 2. Unilateral injections (n = 9) made horizonta l saccades to the injected side hypermetric and those to the other sid e hypometric (mean gain of 1.37 and 0.6 1, respectively, for 10-degree s target steps, and 1.26 and 0.81 for 20-degrees target steps; normal saccade gain was 0.96). Saccades to vertical targets showed a small bu t significant hypermetria and curved strongly toward the side of the i njection. The trajectories and end points of all targeted saccades wer e more variable than normal. 3. After unilateral injections, centripet al saccades were slightly larger than centrifugal saccades (mean gains for ipsilateral saccades were 1.42 and 1.31, respectively, for 10-deg rees target steps, and 1.37 and 1.15 for 20-degrees target steps). 4. Unilateral injections increased the average acceleration of ipsilatera l saccades and decreased the acceleration of contralateral saccades. I njections decreased both the acceleration and deceleration of vertical saccades. 5. After dysmetric saccades, monkeys acquired the target wi th an abnormally high number of hypometric corrective saccades. Inject ion increased the average number of corrective saccades from 0.6 to 2. 1 after 10-degrees horizontal target steps and from 0.8 to 2.1 after 2 0-degrees steps. The size of each successive corrective saccade in a s eries decreased, and the latency from the previous corrective saccade increased. 6. Bilateral injections (n = 2) of muscimol, in which we in jected first into the left caudal fastigial nucleus and then, within 3 0 min, into the right, made all saccades hypermetric (mean gain for 10 -degrees right, left, up, and down saccades was 1. 18, 1.49, 1.43, and 1.10, respectively). Paradoxically, bilateral injection decreased bot h saccade acceleration and deceleration. Saccade trajectories and end points were more variable than normal. 7. To account for the effects o f our injections, we propose that the activity of caudal fastigial neu rons on one side normally helps to decelerate ipsilateral saccades and helps to accelerate contralateral saccades by influencing the feedbac k loop of the saccade burst generator in the brain stem. Without cauda l fastigial activity the brain stem burst generator produces hypermetr ic, variable saccades. We therefore also propose that the influence of caudal fastigial neurons on the burst generator makes saccades more c onsistent and accurate. 8. Our injections caused oculomotor deficits t hat were essentially identical to those of Wallenberg's syndrome. We p ropose that the oculomotor deficits in Wallenberg patients, whose lesi ons are in the lateral medulla, really result from chronic inhibition of caudal fastigial neurons. This inhibition ensues when the medullary lesion interrupts olivocerebellar fibers bound for the part of the ve rmal cortex afferent to the saccade-related fastigial neurons.