L-2-amino-3-phosphonopropionate blocks late synaptic long-term potentiation

The possible involvement of the metabotropic glutamate receptor in mechanisms of hippocampal long-term potentiation was investigated with the new antagonist 2-amino-3-phosphonopropionate (AP3). The action of D-AP3, D,L-AP3 and of the more selective L-isomer was tested on CA1 pyramidal cells in-vitro. If 100-300 microM of L- or D,L-AP3 was present during tetanization, post-tetanic and early long-term potentiation developed almost normally. However, starting from 100 min, LTP of the field-EPSP was eliminated in an irreversible manner. In contrast to the L-isomer, D-AP3 did not influence the course of LTP. These data suggest that the activation of the metabotropic glutamate receptor is necessary for subsequent mechanisms enabling the late maintenance of LTP.