Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation.

Short, high frequency stimulation bursts (4 pulses at 100 Hz) were applied to Schaffer/commissural projections to the CA1 field of rat hippocampal slices at 0.1, 0.2, 1.0 or 2.0-s intervals to assess their efficacy in eliciting long-term potentiation (LTP). Bursts repeated at 2-s intervals induced very little LTP; shorter repetition intervals reliably elicited LTP, with the 200-ms repetition interval producing the greatest potentiation. A short-term potentiation effect, which was maximal 20 s after the last burst and decayed within 10 min, was affected differently by the stimulation parameters than was LTP, suggesting that the two phenomena are due to different processes. The results indicate that patterns of stimulation resembling spike discharge patterns of hippocampal neurons in animals in exploratory situations are effective in inducing LTP and suggest temporal constraints on the mechanisms involved in triggering synaptic plasticity.