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In CA1 stratum oriens of hippocampal slices, a robust long-term potentiation (LTP) induced by tetanic stimulation (20 pulses at 100 Hz, 10 trains delivered at 0.1 Hz) was accompanied by a slowly developing potentiation in a second, untetanized pathway. N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonovaleric acid (D-APV, 50 or 100 microM) reduced the homosynaptic LTP by 80% but failed to affect heterosynaptic LTP. The metabotropic receptor antagonist DL-2-amino-3-phosphonopropionic acid DL-AP3, 300 microM) or (+)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM), applied with DL-APV, further reduced homosynaptic LTP and blocked heterosynaptic LTP. The inhibitor of Ca(2+)-induced Ca2+ release dantrolene (20 microM), also applied with DL-APV, blocked both components of LTP. Importantly, when low-frequency test stimulation (0.017 Hz) to the untetanized, heterosynaptic pathway was interrupted for 30 min after homosynaptic tetanization, heterosynaptic LTP did not develop. These results demonstrate homosynaptic and heterosynaptic LTP inductions in stratum oriens of the area CA1 and suggest that the heterosynaptic LTP is induced by NMDA-independent, novel associative processes between tetanized and untetanized pathways.

Long-term potentiation and evidence for novel synaptic association in CA1 stratum oriens of rat hippocampus.