Long-term potentiation in hippocampal CA1: effects of afterdischarges, NMDA antagonists, and anticonvulsants

Long-term potentiation (LTP) of the basal dendritic population excitatory postsynaptic potential (EPSP) in hippocampal CA1 was readily elicited in behaving rats, without afterdischarges (ADs), by theta-frequency-patterned primed bursts (PBs) delivered to the contralateral CA1. A long-lasting postictal potentiation (PIP) was also elicited by high-frequency trains (1 s at 200 Hz), following an AD and a 5- to 10-min depression. The N-methyl-D-aspartate (NMDA) antagonist 2-amino-phosphonovalerate was effective in blocking both LTP and PIP. The noncompetitive NMDA antagonist MK801 (0.5 mg/kg ip) attenuated the PB-induced LTP but enhanced PIP. The anticonvulsants phenytoin (40 mg/kg ip) and U54494A (25 or 50 mg/kg ip) had no effects on the LTP induced by a PB but they, like MK801, enhanced PIP to various degrees. The apparent enhancement of PIP by anticonvulsants may be a direct result of shortening the hippocampal AD duration and alleviation of the postictal EPSP depression. It is inferred that the typical hippocampal AD did not induce potentiation, but rather a postictal depression of the EPSP or a suppression of LTP. The mechanism of the postictal depression is likely different from the NMDA receptor-mediated LTP and PIP and it may depend on the AD duration (and perhaps excessive CA2+ influx) but not critically on NMDA receptors.