GABAergic modulation of neocortical long-term potentiation in the freely moving rat

Although the neocortex has generally been considered resistant to the induction of long-term potentiation (LTP), we have recently shown that LTP can be reliably induced in the freely moving rat provided that the stimulation sessions are spaced and repeated. Here, we report that the induction of LTP in this preparation can be modulated by both GABAergic agonism and antagonism. The delivery of stimulation trains in the presence of the GABA(A) agonist diazepam blocked the induction of neocortical LTP, while the GABA(A) antagonist picrotoxin slowed the development of potentiation. When animals that had previously received high-frequency stimulation combined with diazepam were repotentiated, they showed greater resistance to LTP induction than animals that had received diazepam alone. These data suggest that the inhibitory circuits themselves may have potentiated. The demonstration that diazepam blocks neocortical LTP provides further support for the notion that LTP plays a role in memory formation.