The role of presynaptic calcium in short-term enhancement at the hippocampal mossy fiber synapse

The mossy fiber synapse between dentate granule cells and CA3 pyramidal cells in the guinea pig hippocampus shows a robust short-term synaptic enhancement. We have simultaneously measured presynaptic residual free calcium ([Ca²⁺](i)) and postsynaptic field potentials at this synapse to examine the role of [Ca²⁺](i) in this enhancement. Single action potentials produced an increase in [Ca²⁺](i) of 10-50 nM that decayed to resting levels with a time constant of about 1 sec. Trains of action potentials produced larger [Ca²⁺](i) increases that returned more slowly to resting levels. Following the onset of moderate frequency stimulus trains (0.1-5 Hz), synaptic transmission and [Ca²⁺](i) both increased and eventually plateaued. During the steady-state phase a linear relationship between [Ca²⁺](i) and synaptic enhancement was observed. During the initial buildup, however, [Ca²⁺](i) rose more rapidly than synaptic enhancement. Similarly, during the decay phase immediately following termination of a stimulus train, [Ca²⁺](i) returned to prestimulus levels faster than synaptic enhancement. High concentrations of the calcium buffer EGTA in the presynaptic terminal slowed the buildup and decay of both [Ca²⁺](i) and synaptic enhancement produced by stimulus trains. Under these conditions, the time course of [Ca²⁺](i) and synaptic enhancement were well matched. This suggests that, despite the differences in kinetic rates observed for normal buffering conditions, increases in [Ca²⁺](i) play a causal role in short- term enhancement. An increase in [Ca²⁺](i) of 10-30 nM produced a twofold enhancement. We propose a simple kinetic model to explain these results. The model assumes that synaptic enhancement is controlled by a Ca-dependent first-order reaction. According to this scheme, a change in [Ca²⁺](i) alters neurotransmitter release, but the slow kinetics of the underlying reaction introduces a temporal filter, producing a delay in the change in synaptic enhancement.