Target-Cell Specificity of Kainate Autoreceptor and Ca2+-Store-Dependent Short-Term Plasticity at Hippocampal Mossy Fiber Synapses

Presynaptic kainate receptors (KARs) modulate transmission between dentate granule cells and CA3 pyramidal neurons. Whether presynaptic KARs affect other synapses made by granule cell axons [mossy fibers (MFs)], on hilar mossy cells or interneurons, is not known. Nor is it known whether glutamate release from a single MF is sufficient to activate these receptors. Here, we monitor Ca2+ in identified MF boutons traced from granule cell bodies. We show that a single action potential in a single MF activates both presynaptic KARs and Ca2+ stores, contributing to use-dependent facilitation at MF-CA3 pyramidal cell synapses. Rapid local application of kainate to the giant MF bouton has no detectable effect on the resting Ca2+ but facilitates action-potential-evoked Ca2+ entry through a Ca2+ store-dependent mechanism. Localized two-photon uncaging of the Ca2+ store receptor ligand IP3 directly confirms the presence of functional Ca2+ stores at these boutons. In contrast, presynaptic Ca2+ kinetics at MF synapses on interneurons or mossy cells are insensitive to KAR blockade, to local kainate application or to photolytic release of IP3. Consistent with this, postsynaptic responses evoked by activation of a single MF show KAR-dependent paired-pulse facilitation in CA3 pyramidal cells, but not in interneurons or mossy cells. Thus, KAR-Ca2+ store coupling acts as a synapse-specific, short-range autoreceptor mechanism.