Figure 1. Kainate receptors modulate short-term plasticity of presynaptic Ca2+ entry at individual MF–CA3 pyramidal cell synapses involving rapid Ca2+ release from Ca2+ stores. A, A granule cell axon traced from the soma (Alexa Fluor 594 emission, collage; see Materials and Methods); the CA3 giant bouton of interest is marked by a dashed frame and enlarged in C. B, Examples of giant MF boutons traced in area CA3, 300–700 μm from cell bodies. C–D, In the giant bouton shown in C (also A), five action potentials at 20 Hz (arrows) evoke clear Ca2+-dependent fluorescence signals (line-scans in D, Fluo-4 emission; 10-sweep average), in the presence of 20 μm GYKI53655 (GYKI), and after application of NBQX, as indicated. Line scan positioning is shown in C by dotted arrows. E, The average time course for the effect of KAR blockade by NBQX (in the presence of GYKI, n = 10) on the paired-pulse ratio of action-potential-evoked Ca2+ responses, PPR = (ΔF/F)2/(ΔF/F)1. Error bars, SEM. F–G, Blocking KARs with NBQX (F) or with 10 μm UBP302 (G) has little effect on the resting Ca2+ fluorescence Frest but decreases PPR. Traces, characteristic line-scans (10-sweep average), as indicated. Bar plots, statistical summary: average change relative to control (open circles, individual experiments);*p < 0.04; **p < 0.01; ***p < 0.005. H–I, Ca2+ store blockade by 50 μm ryanodine in control conditions reduces PPR (H) whereas the presence of NBQX completely occludes this effect (I). In both cases, ryanodine increases resting Ca2+ fluorescence Frest (note that traces are baseline-normalized). *p < 0.03; ***p < 0.002. Other notations are the same as in F–G.