Kainate receptors are involved in synaptic plasticity.
The ability of synapses to modify their synaptic strength in response to activity is a fundamental property of the nervous system and may be an essential component of learning and memory. There are three classes of ionotropic glutamate receptor, namely NMDA (N-methyl-D-aspartate), AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole-4-propionic acid) and kainate receptors; critical roles in synaptic plasticity have been identified for two of these. Thus, at many synapses in the brain, transient activation of NMDA receptors leads to a persistent modification in the strength of synaptic transmission mediated by AMPA receptors. Here, to determine whether kainate receptors are involved in synaptic plasticity, we have used a new antagonist, LY382884 ((3S, 4aR, 6S, 8aR)-6-((4-carboxyphenyl)methyl-1,2,3,4,4a,5,6,7,8,8a-decahydro isoquinoline-3-carboxylic acid), which antagonizes kainate receptors at concentrations that do not affect AMPA or NMDA receptors. We find that LY382884 is a selective antagonist at neuronal kainate receptors containing the GluR5 subunit. It has no effect on long-term potentiation (LTP) that is dependent on NMDA receptors but prevents the induction of mossy fibre LTP, which is independent of NMDA receptors. Thus, kainate receptors can act as the induction trigger for long-term changes in synaptic transmission.
Bortolotto
Z A
ZA
MRC Centre for Synaptic Plasticity, Department of Anatomy, Medical School, University of Bristol, UK.
Clarke
V R
VR
Delany
C M
CM
Parry
M C
MC
Smolders
I
I
Vignes
M
M
Ho
K H
KH
Miu
P
P
Brinton
B T
BT
Fantaske
R
R
Ogden
A
A
Gates
M
M
Ornstein
P L
PL
Lodge
D
D
Bleakman
D
D
Collingridge
G L
GL
D000818:Animals; D002460:Cell Line; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D019599:Mossy Fibers, Hippocampal / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism; D009435:Synaptic Transmission
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D007736:Kynurenic Acid; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; C400802:LY382884