Post-activation potentiation in the neocortex. IV. Multiple sessions required for induction of long-term potentiation in the chronic preparation.

The neocortex in chronically prepared rats is very resistant to the induction of long-term potentiation (LTP). In the first of two experiments described in this paper, we tried unsuccessfully to induce neocortical LTP within one session by coactivating basal forebrain cholinergic and cortical inputs to our neocortical recording site. In the second experiment, we tested a new procedure which involved the application of repeated conditioning sessions over several days. This procedure was suggested by our finding that kindling-induced potentiation (KIP) of cortical field potentials could be reliably triggered but was slow to develop. We administered 30 high frequency trains per day to the corpus callosum for 25 days. LTP in callosal-neocortical field potentials became clear after about 5 days of stimulation and reached asymptotic levels by about 15 days. After the termination of treatment, LTP persisted for at least 4 weeks, the duration of our post-stimulation test period. As in previous experiments on kindling-induced potentiation, the potentiation effects were clear in both early population spike components and in a late (probably disynaptic) component. The monosynaptic EPSP component was often depressed, but this may have been due to competing field currents generated by the enhanced population spike activity. We discuss these results in the context of theories emphasizing slower but more permanent memory storage in neocortex compared to the hippocampus.