THE ROLE OF PRESYNAPTIC CALCIUM IN SHORT-TERM ENHANCEMENT AT THE HIPPOCAMPAL MESSY FIBER SYNAPSE

The messy fiber synapse between dentate granule cells and CA3 pyramida l cells in the guinea pig hippocampus shows a robust short-term synapt ic enhancement. We have simultaneously measured presynaptic residual f ree calcium ([Ca2+](i)) and postsynaptic field potentials at this syna pse to examine the role of [Ca2+](i) in this enhancement. Single actio n potentials produced an increase in [Ca2+](i) of 10-50 nM that decaye d to resting levels with a time constant of about 1 sec. Trains of act ion potentials produced larger [Ca2+](i) increases that returned more slowly to resting levels. Following the onset of moderate frequency st imulus trains (0.1-5 Hz), synaptic transmission and [Ca2+](i) both inc reased and eventually plateaued. During the steady-state phase a linea r relationship between [Ca2+](i) and synaptic enhancement was observed . During the initial buildup, however, [Ca2+](i) rose more rapidly tha n synaptic enhancement. Similarly, during the decay phase immediately following termination of a stimulus train, [Ca2+](i) returned to prest imulus levels faster than synaptic enhancement. High concentrations of the calcium buffer EGTA in the presynaptic terminal slowed the buildu p and decay of both [Ca2+](i) and synaptic enhancement produced by sti mulus trains. Under these conditions, the time course of [Ca2+](i) and synaptic enhancement were well matched. This suggests that, despite t he differences in kinetic rates observed for normal buffering conditio ns, increases in [Ca2+](i) play a causal role in short-term enhancemen t. An increase in [Ca2+](i) of 10-30 nM produced a twofold enhancement . We propose a simple kinetic model to explain these results. The mode l assumes that synaptic enhancement is controlled by a Ca-dependent fi rst-order reaction. According to this scheme, a change in [Ca2+](i) al ters neurotransmitter release, but the slow kinetics of the underlying reaction introduces a temporal filter, producing a delay in the chang e in synaptic enhancement.