Selective enhancement of non-NMDA receptor-mediated responses following induction of long-term potentiation in entorhinal cortex

The contribution of NMDA receptors to the expression of long-term potentiation (LTP) is controversial. In entorhinal cortex (EC) previous studies reported either that LTP was exclusively expressed through NMDA receptors or that both NMDA and non-NMDA receptors were involved in LTP expression. To reexamine this issue, horizontal entorhinal cortical slices were prepared from adult rats and electrical stimulation was delivered in layer II/III, while field potential recordings were made in layer III. In the standard condition (2.5 mM Mg(++)), LTP was reliably induced by theta burst stimulation, but was blocked by 100 microM D-AP5, an NMDA receptor antagonist. This corroborates previous reports that NMDA receptor activation is required for induction of EC LTP. The field potential response was not affected by D-AP5, but completely blocked by 10 microM CNQX, a non-NMDA receptor antagonist. This indicates that the expression of LTP is mediated by non-NMDA receptors in the standard condition. LTP of NMDA receptor-mediated responses was tested by comparing NMDA responses before and after applying theta burst stimulation in medium containing low magnesium (0.4-1 mM). Theta burst stimulation induced 43.2+/-9.7% increase of non-NMDA responses (i.e., AP5-insensitive fast component) but 5.6+/-9.0% decrease of the NMDA receptor component (AP5-sensitive slow component). These results indicate that activation of NMDA receptors is critical for induction of LTP, but LTP expression is mediated by non-NMDA receptors in EC under these experimental conditions.