Kainate receptors are involved in synaptic plasticity (vol 402, pg 297, 1999)

The ability of synapses to modify their synaptic strength in response to ac tivity is a fundamental property of the nervous system and may be an essent ial component of learning and memory(1). There are three classes of ionotro pic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (alpha -am ino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors( 2); critical roles in synaptic plasticity have been identified for two of t hese. Thus, at many synapses in the brain, transient activation of NMDA rec eptors leads to a persistent modification in the strength of synaptic trans mission mediated by AMPA receptors(3,4). Here, to determine whether kainate receptors(5-7) are involved in synaptic plasticity, we have used a new ant agonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a ,5,6,7,8,8a-decahydroisoquinoline-3-carboxylic acid), which antagonizes kai nate receptors at concentrations that do not affect AMPA or NMDA receptors. We rnd that LY382884 is a selective antagonist at neuronal kainate recepto rs containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mo ssy fibre LTP, which is independent of NMDA receptors. Thus, kainate recept ors can act as the induction trigger for longterm changes in synaptic trans mission.