TEA elicits two distinct potentiations of synaptic transmission in the CA1 region of the hippocampal slice

Abstract

Extracellular application of tetraethylammonium (TEA) has been shown to elicit a prolonged synaptic potentiation in the CA1 region of the hippocampus that is unaffected by NMDA receptor antagonists, but is blocked by antagonists to voltage-dependent calcium channels (Aniksztejn and Ben-Ari, 1991; Huang and Malenka, 1993). In the present study the relation between TEA-induced potentiation and NMDA receptor-dependent long-term potentiation (LTP) was investigated in the CA1 region of the hippocampal slice using extracellular recordings and picrotoxin to block GABA(A)-mediated inhibition. Consistent with the finding of Huang and Malenka (1993), NMDA receptor- dependent LTP partially occluded the TEA-induced potentiation. However, this occlusion was abolished when the NMDA receptor antagonist D(-)-2-amino-5- phosphonopentanoic acid (D-AP5) was present during the application of TEA, indicating one component of TEA-induced potentiation that is induced via NMDA receptor channels and another component that is distinct from NMDA receptor- dependent LTP. In the presence of antagonists to voltage-dependent calcium channels (nifedipine or nifedipine/flunarazine) application of TEA induced a potentiation that was largely occluded by NMDA receptor-dependent LTP. In common with NMDA receptor-dependent LTP, the TEA-induced potentiation, elicited in the presence of antagonists to voltage-dependent calcium channels, was associated with a symmetrical increase of the field EPSP. On the other hand, the TEA-induced potentiation elicited in the presence of D- AP5 produced an increase of the field EPSP that did not include the early part of the initial slope. It is concluded that application of TEA can activate both NMDA receptor channels and voltage-dependent calcium channels, and that the potentiation associated with activation of voltage-dependent calcium channels is distinct from NMDA receptor-dependent LTP.