BLOCK OF THETA-BURST-INDUCED LONG-TERM POTENTIATION BY (1S,3S)-1-AMINOCYCLOPENTANE-1,3-DICARBOXYLIC ACID - FURTHER EVIDENCE AGAINST LONG-TERM POTENTIATION AS A MODEL FOR LEARNING

It has been previously reported that block of high-frequency stimulati on-induced long-term potentiation of synaptic transmission in the hipp ocampus does not necessarily lead to impairment of spatial learning. H erl we show that (1S,3S)-1-aminocyclopentane-1,3-dicarboxylic acid, an agonist at group II metabotropic glutamate receptors, completely bloc ked long-term potentiation induced by a theta-burst type of stimulatio n protocol (five pulses at 75 Hz per train, 200 ms inter-train interva l) in the CA1 region in vivo. The drug did not significantly affect sy naptic responses during each train whereas inter-train facilitation of excitatory postsynaptic potentials was slightly reduced. It also prod uced a large reduction in paired-pulse facilitation (50 ms inter-stimu lus interval), possibly indicating that an increase in inhibition migh t be involved in the block of long-term potentiation. The drug dose us ed (5 mu l of a 10 mM solution i.c.v.) was half the dose which inhibit ed high-frequency stimulation-induced long-term potentiation in earlie r experiments but which did not prevent learning of spatial tasks. We conclude that long-term potentiation induced by a more physiological s timulation protocol which uses theta-like inter-train intervals does n ot appear to accurately model the synaptic changes which are believed to occur during learning either. (C) 1997 IBRO. Published by Elsevier Science Ltd.