It is currently unknown why glutamatergic presynaptic terminals express multiple types of glutamate receptors. We have addressed this question by studying both acute and long-term regulation of mossy fibre function in the hippocampus. We find that inhibition of both mGlu 1 and mGlu 5 receptors together can block the induction of mossy fibre LTP. Furthermore, mossy fibre LTP can be induced by the pharmacological activation of either mGlu 1 or mGlu 5 receptors, provided that kainate receptors are also stimulated. Like conventional mossy fibre LTP, chemically-induced mossy fibre LTP (chem-LTPm) depends on Ca 2+ release from intracellular stores and the activation of PKA. Similar synergistic interactions between mGlu receptors and kainate receptors were observed at the level of Ca 2+ signalling in individual giant mossy fibre boutons. Thus three distinct glutamate receptors interact, in both an AND and OR gate fashion, to regulate both immediate and long-term presynaptic function in the brain.
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