Electrical stimuli patterned after the theta-rhythm induce multiple forms of LTP

The induction of long-term potentiation (LTP) by high-frequency stimulation is considered an acceptable model for the study of learning and memory. In area CA1 calcium influx through N-methyl-D-aspartate receptors (NMDARs; nm daLTP) and/or L-type voltage-dependent calcium channels (vdccLTP) results i n distinct forms of LTP. In the light of significant accumulation of knowle dge about patterns of naturally occurring activity in the intact animal, we examined whether the application of stimuli patterned after natural activi ty induced nmdaLTP and/or vdccLTP. In rat hippocampal slices we examined LT P induced by three types of patterned stimulation short (S-TBS), long (L-TB S), and high-intensity long theta-patterned stimulation (HL-TBS). The patte rns of stimulation were applied in control, nifedipine (blocks vdccLTP), D, L-2-amino-5-phosphonovaleric acid (APV; blocks nmdaLTP), or APV and nifedip ine containing media. We found that S-TBS resulted in LTP that was complete ly attenuated in the presence of APV but was unaffected by nifedipine. Thus S-TBS results in the selective induction of nmdaLTP. L-TBS resulted in LTP that was completely blocked by APV and only partially blocked by nifedipin e. Therefore L-TBS results in a compoundLTP consisting of both nmdaLTP and vdccLTP components. In the presence of APV, HL-TBS resulted in vdccLTP, and when APV and nifedipine were both present, LTP was completely blocked. Thu s HL-TBS results in a vdccLTP in isolation when APV is present. We also exa mined saturation of S-TBS-induced LTP (nmdaLTP) by applying S-TBS at short intervals. When nifedipine was present, multiple S-TBS trains resulted in a substantially smaller final LTP as compared with controls. We conclude tha t multiple bursts of S-TBS eventually summate to result in compoundLTP. Sti muli patterned after innate rhythms in the hippocampus effectively induce n mdaLTP (S-TBS), compoundLTP (L-TBS), or vdccLTP (HL-TBS).