Delayed response deficit in monkeys by locally disturbed prefrontal neuronal activity by bicuculline

Effects of local injection of a gamma-aminobutyric acid antagonist, bicuculline (10-30 micrograms dissolved in saline) in the principal prefrontal cortex on the delayed response task were investigated in two monkeys. On a visual Go signal, the monkeys rotated a handle to the left or to the right (Go period) according to a visual cue (left or right; 1 s) presented 4 s earlier. Bicuculline induced bursting activity at the injected site 1-2 min after the injection and 5 min later the burst activity spread to nearby cortical areas (less than 4 mm diameter). Within 5 min after injection, the monkeys showed errors in Go periods, rotating the handle to the contralateral zone, regardless of the cue side. This tendency continued for 30-40 min and returned to the control level. Electromyographic recordings of forearm muscles did not show any changes. The effect was observed when the drug was injected into a circumscribed area of the bottom of the mid-principalis region. It appears that disturbed neuronal activity in a small group of cortical columns induces performance errors of specific direction of the delayed response.