GABAergic inhibition of neuronal activity in the primate motor and premotor cortex during voluntary movement.

1. The functional role of GABAergic inhibition in neuronal activity in the forearm-hand area of the motor cortex and the postarcuate premotor cortex was studied while monkeys pressed and released a lever in response to a visual cue. gamma-Aminobutyric acid (GABA), its agonist muscimol (MUS), and its antagonist bicuculline methiodide (BMI), as well as acetylcholine, noradrenaline, and sodium glutamate, were applied iontophoretically to isolated single neurons whose activity was recorded via glass micropipettes that contained carbon fibers. 2. The activity from single neurons recorded in the motor and premotor cortex showed changes during the press or release of the lever by movement of the contralateral wrist. Discharge of most of the movement-related neurons (greater than 90%) was decreased or completely suppressed by iontophoretically applied GABA or MUS. 3. The activity of the movement-related neurons increased after application of BMI. In 70% of neurons tested, the activity during application of BMI was specifically enhanced at or near the phase of their peaks of activity, with or without a noticeable elevation in background activity. 4. About 10% of the neurons that had been unidirectional (i.e., neurons that showed a change in activity at either the lever-press or lever-release phase) became bidirectional (i.e., they showed changes in activity at both phases) when GABA transmission was blocked by the application of BMI. Bidirectional neurons also showed a reduction in the value of the directionality index. 5. One-half of the silent neurons, which had not shown any activity during either the lever-release or the lever-press phase, became active during the movement phases that followed application of BMI. 6. Most of the cortical neurons in layers II-VI in the motor area were found to be subject to GABAergic inhibition during voluntary movement. 7. We conclude that GABAergic inhibition plays a role in regulating the population of task-related neurons, and the levels of the task-related activity. GABAergic inhibition also improves directionality index in the motor cortex neurons to control the activity of target muscles.