Presynaptic kainate receptors at hippocampal mossy fiber synapses

Hippocampal mossy fibers, which are the axons of dentate granule cells, for m powerful excitatory synapses onto the proximal dendrites of CA3 pyramidal cells. It has long been known that high-affinity binding sites for kainate , a glutamate receptor agonist, are present on mossy fibers. Here we summar ize recent experiments on the role of these presynaptic kainate receptors ( KARs). Application of kainate has a direct effect on the amplitude of the e xtracellularly recorded fiber volley, with an enhancement by low concentrat ions and a depression by high concentrations. These effects are mediated by KARs, because they persist in the presence of the alpha -amino-3-hydroxy-5 -methyl-4-isoxazolepropionic acid receptor-selective antagonist GYK1 53655, but are blocked by the alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropioni c acid/KAR antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and the KAR anta gonist SYM2081. The effects on the fiber volley are most likely caused by a depolarization of the fibers via the known ionotropic actions of KARs, bec ause application of potassium mimics the effects. In addition to these effe cts on fiber excitability, low concentrations of kainate enhance transmitte r release, whereas high concentrations depress transmitter release. Importa ntly, the synaptic release of glutamate from mossy fibers also activates th ese presynaptic KARs, causing an enhancement of the fiber volley and a faci litation of release that lasts for many seconds. This positive feedback con tributes to the dramatic frequency facilitation that is characteristic of m ossy fiber synapses. It will be interesting to determine how widespread fac ilitatory presynaptic KARs are at other synapses in the central nervous sys tem.