Abstract
Kainate receptors (KARs) are poorly understood subtype of ionotropic glutamate receptors distributing widely and heterogeneously in the central nervous system (CNS). Recent studies elucidated the roles of KARs in activity-dependent modulation of synaptic transmission at certain synapses in the CNS, including hippocampal mossy fiber synapses where KAR subunits are most abundantly expressed. An important notice of these studies is that these receptors localize not only on postsynaptic but also on presynaptic membrane, and these presynaptic KARs impart an 'presynaptic' associativity to mossy fiber long-term potentiation (MF-LTP), an unusual form of plasticity that is independent of NMDA receptor activation and is expressed presynaptically. Homosynaptic as well as heterosynaptic positive feedback regulation of transmitter release via presynaptic KARs provides a novel way of signaling at the central synapses. To examine the cellular mechanism of activity-dependent modulation by presynaptic KARs, we adopted optical methods to monitor presynaptic Ca2+ and voltage transients at the mossy fiber synapses. We revealed that activation of presynaptic KARs elicits prominent depolarization of the presynaptic terminals and causes use-dependent facilitation of presynaptic Ca2+ influx by an action potential. Thus, presynaptic KARs at the mossy fiber synapses amplify presynaptic Ca2+ rise during repeated stimuli, and thereby affect the threshold of induction of MF-LTP. [Jpn J Physiol 54 Suppl:S33 (2004)]