Loss of kainate receptor-mediated heterosynaptic facilitation of mossy-fiber synapses in KA2-/- mice.
Multimeric assemblies of kainate (KA) receptor subunits form glutamate-gated ion channels that mediate EPSCs and function as presynaptic modulators of neurotransmitter release at some central synapses. The KA2 subunit is a likely constituent of many neuronal kainate receptors, because it is widely expressed in most neurons in the CNS. We have studied the effect of genetic ablation of this receptor subunit on synaptic transmission at the mossy-fiber-CA3 pyramidal cell synapse in hippocampal slices, where kainate receptors are localized to both presynaptic and postsynaptic sites. We found that both postsynaptic and presynaptic mossy-fiber kainate receptor function is altered in neurons from KA2-/- mice. The presynaptic facilitatory autoreceptor, which modulates glutamate release from mossy-fiber terminals, had a reduced affinity for exogenous agonists and synaptic glutamate. Although presynaptic facilitation attributable to homosynaptic glutamate release was normal at mossy-fiber synapses in KA2-/- neurons, heterosynaptic kainate receptor-mediated facilitation resulting from the spillover of glutamate from CA3 collateral synapses was absent. Consistent with a decrease in glutamate affinity of the receptor, the half-decay of the postsynaptic kainate-mediated EPSC was shorter in the knock-out mice. These results identify the KA2 subunit as a determinant of kainate receptor function at presynaptic and postsynaptic mossy-fiber kainate receptors.
Contractor
Anis
A
Molecular Neurobiology Laboratory, The Salk Institute for Biological Studies, La Jolla, California 92037, USA. contractor@salk.edu
Sailer
Andreas W
AW
Darstein
Melanie
M
Maron
Cornelia
C
Xu
Jian
J
Swanson
Geoffrey T
GT
Heinemann
Stephen F
SF
D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D007608:Kainic Acid / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D021122:Protein Subunits / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D018691:Excitatory Amino Acid Antagonists; D007608:Kainic Acid; D021122:Protein Subunits; D018092:Kainic Acid Receptors