Removal of extracellular calcium after conditioning stimulation disrupts long-term potentiation in the CA1 region of rat hippocampal slices

During a conditioning stimulus, the influx of Ca²⁺ into neurons appears to be crucial for the induction of long-term potentiation at CA1 hippocampal synapses. We report here that extracellular Ca²⁺ is also required for full production of long-term potentiation during a critical period following the conditioning stimulus. In control slices, removal of extracellular Ca²⁺ (0 mM Ca²⁺/10 mM Mg²⁺) for 15 min eliminated synaptic transmission. Following reintroduction of normal extracellular solution, synaptic responses recovered fully within 15 min. However, removal of extracellular Ca²⁺ 15-30 min after theta burst stimulation significantly decreased the magnitude of long-term potentiation. A time window seems to exist for this effect, since either earlier or later Ca²⁺ removal was less effective. The effect of the 0 mM Ca²⁺/10 mM Mg²⁺ solution was observed in the absence of afferent stimulation, suggesting that evoked synaptic activity is not required. Perfusion with an extracellular solution containing Cd²⁺ (40 μM), a broad spectrum inhibitor of voltage-dependent Ca²⁺ channels, or a low concentration (50 μM) of Ni²⁺, which preferentially blocks T-type, low-voltage-activated Ca²⁺ channels, also caused a significant decrease in potentiation, whereas an inhibitor of L-type, high voltage-activated Ca²⁺ channel, nifedipine (20 μM), had no effect. These results suggest that the presence of extracellular Ca²⁺ during a specific period after high-frequency synaptic activity is necessary for the maintenance of long-term potentiation, and that voltage-gated Ca²⁺ channels play a role in the stabilization of synaptic plasticity.