Depotentiation of vdccLTP requires NMDAR activation

Long-term potentiation is an enduring increase in synaptic efficacy followi ng repeated stimulation of afferent fibers that is thought to underlie memo ry. In area CAI of the hippocampus at least two forms of synaptic potentiat ion coexist at the same synapses; nmdaLTP and vdccLTP. NmdaLTP is induced b y Ca2+ entry through NMDARs and is dependent on serine/threonine kinase act ivation, while vdccLTP is induced through Ca2+ entry through VDCCs and is d ependent on tyrosine kinase activation. Depotentiation is a mechanism known to reverse nmdaLTP through phosphatase activation. The depotentiation of v dccLTP has not been previously investigated. We used hippocampal slices (ar ea CAI) from male Long-Evans rats to induce vdccLTP with a 200-Hz tetanus i n the presence of 50 AM PV. The 200-Hz tetanus resulted in a slowly develop ing vdccLTP that remained stable for at least 30 min. Thirty minutes after vdccLTP was induced, a low-frequency tetanus (3, 10, 20, 30, or 40 Hz) was applied in the presence of APV in an attempt to depotentiate vdccLTP. The 3 - and 10-Hz low-frequency tetani resulted in no depotentiation. The 20- and 30-Hz tetani partially depotentiated vdccLTP (by similar to 13%), whereas the 40-Hz tetanus resulted in further potentiation. When APV was washed out prior to the 3-Hz low-frequency tetanus, the vdccLTP was completely depote ntiated-presumably by NMDAR mechanisms. Our results indicate that vdccLTP i s resistant to depotentiation under low-frequency stimulation conditions th at readily depotentiate nmdaLTP. As tetanus frequencies are increased a sma ll depotentiation is observed, suggesting that vdccLTP can be depotentiated to a small extent. When NMDARs are unblocked, vdccLTP can be completely de potentiated by a 3-Hz low-frequency tetanus, suggesting that vdccLTP can be depotentiated via activation of NMDAR mechanisms. (C) 2001 Academic Press.