Cholinergic modulation of neocortical long-term potentiation in the awake, freely moving rat.

The neocortex has proven resistant to LTP induction using standard in vitro and acute, in vivo preparations. Because the neocortex is widely thought to be involved in long-term information storage, this resistance raises questions about the validity of LTP as a memory model. Recently, we have shown that the neocortex of freely moving rats reliably supports LTP, provided that the stimulation is spaced and repeated over days. The following experiments were designed to evaluate the neuromodulatory role played by cholinergic systems in the induction of LTP in this preparation. Chronically implanted rats received either low- or high-intensity LTP-inducing tetani in combination with the administration of either a cholinergic agonist or antagonist injected systemically. Potentiation was evidenced as amplitude changes in both early and late components of the evoked field potential, the former including population spikes. The cholinergic agonist facilitated LTP induction in the late component of both high- and low-intensity groups. The cholinergic antagonist blocked LTP induction in the early component of the high-intensity group. The possibility that there are component-specific modulatory effects of cholinergic agents on the induction of neocortical LTP is discussed.