Application of the GABA antagonist bicuculline to the premotor cortex reduces the ability to withhold reaching movements by well-trained monkeys in visually guided reaching task.

1. A gamma-aminobutyric acid (GABA) antagonist, bicuculline methiodide (BMI, 10 micrograms/microliters, 1 microliter), was locally injected into a total of 32 sites in the right premotor cortex (PM) of two rhesus monkeys that had been well-trained in a visually guided reaching task (VR) for approximately 3 yr. The monkey initiated the task by pressing a central hold lever with its left hand, and this was followed by waiting (1 s), warning (central green square on a computer monitor, 0.5 s), cue (right, upper, or left square), delay (2-5 s), and go (central green square changes to red, < 1.2 s) periods. In the go period, the monkey released the hold lever and reached out to one of three target levers (left, upper, or right) that had been indicated 2-5 s previously in the cue period. 2. At three sites in the dorsal part of the PM, after the local application of BMI, reaching movements of the left forelimb, which were not part of the trained-reaching, occurred 200-300 ms after the onset of a burst of neuronal activity at the BMI injection site. This induced-reaching, which was designated a "forced-reaching" movement, occurred while the monkeys were pressing the hold lever before the cue appeared-i.e., during the waiting or waiting period. No reaching occurred when the burst did not appear. Furthermore, trajectories and electromyograms of the forelimbs during the forced-reaching movements were similar to those in the trained-reaching movements in the VR task. 3. These results suggest that restricted sites in the dorsal PM of monkeys are involved in the initiation and/or execution of trained-reaching movements and that GABAergic inhibition at these sites normally suppresses this initiation/execution unless it is required. By relaxing GABAergic suppression, the dorsal PM might send a command to a neuronal system that is associated with trained reaching to recruit the system, thereby initiating and/or executing the trained reaching.