GABA(A) receptors determine the temporal dynamics of memory retention

Four experiments studied the role of GABA(A) receptors in the temporal dynamics of memory retention. Memory for an active avoidance response was a nonmonotonic function of the retention interval. When rats were tested shortly (2 min) or some time (24 h) after training, retention was excellent, but when they were tested at intermediate intervals (1-4 h), retention was poor. Activity at GABA(A) receptors was critical for impairing memory retention at the intermediate intervals because injection of the GABA(A) receptor partial inverse agonist FG7142 prior to test significantly improved performance. These retention enhancing effects of FG7142 were dose-dependent and not due to any nonspecific effects of FG7142 on activity. Our results suggest that the temporal dynamics of memory retention may be caused by variations in neurotransmission through the GABA(A) receptor in the post-training period.