The time course of Cai governs delayed transmitter release at MLI-MLI synapses. A, Predicted averaged Cai time course. The black solid trace presents the simulated Cai decay after a 50 Hz train of four APs, in the absence of the calcium indicator. The simulation parameters are a resting Cai of 40 nm, Caload of 11 μm/AP, 150 μm PV, 60 μm OG1-like buffer, and extrusion kinetic constants of k1 = 1100 sec-1 and k-1 = 0.022 sec-1. This Cai decay is characterized by a biexponential decay (τf, 39 msec; τs, 626 msec; corresponding amplitude coefficients, 144 and 29 nm). The black dashed trace presents the decay simulated with the same parameters after a 50 Hz train of 10 APs. The Cai decay for the PV-free conditions (gray solid trace, 4-AP train; dotted gray trace, 10-AP train) used the following simulation parameters: resting Cai of 40 nm, Ca2+ load of 11 μm per AP; 60 μm OG1-like buffer; extrusion rates of k1 = 550 sec-1 and k-1 = 0.011 sec-1. Traces have been truncated at 250 nm to highlight differences in the slow decay phase. B, Comparison of delayed transmitter release in WT and PV(-/-) mice. B1, Representative recording of currents obtained from a P20 WT MLI. The arrowhead indicates the onset of a 50 Hz train of 10 presynaptic stimulations. B2, Expanded view of the recording during the stimulation train, as denoted by the dashed line with the arrow in B1. B3, B4, Representative experiment from a P20 PV(-/-) interneuron. Glutamatergic activity has been blocked as detailed in Materials and Methods. C1, C2, Histograms of the temporal evolution of the mean frequency of synaptic events over the prestimulus frequency, pooled from nine WT and six PV(-/-) interneurons (P19-P21). The error bars represent the SEM. Time 0 corresponds to the end of the extracellular stimulation. The gray traces display the Cai time course calculated for a 50 Hz train of 10 APs in A. Values for the WT group were significantly different from one (p < 0.05) for all time bins. For the PV(-/-) group, only the first two time bins have a similar statistical significance.