title: Homeostatic control of synaptic transmission by distinct glutamate receptors.
abstract: Glutamate is the most abundant excitatory neurotransmitter in the brain, and distinct classes of glutamate receptors coordinate synaptic transmission and spike generation upon various levels of neuronal activity. However, the mechanisms remain unclear. Here, we found that loss of synaptic AMPA receptors increased kainate receptor activity in cerebellar granule cells without changing NMDA receptors. The augmentation of kainate receptor-mediated currents in the absence of AMPA receptor activity is required for spike generation and is mediated by the increased expression of the GluK5 high-affinity kainate receptor subunit. Increase in GluK5 expression is sufficient to enhance kainate receptor activity by modulating receptor channel properties, but not localization. Furthermore, we demonstrate that the combined loss of the AMPA receptor auxiliary TARPγ-2 subunit and the GluK5 subunit leads to early mouse lethality. Our findings reveal mechanisms mediated by distinct classes of postsynaptic glutamate receptors for the homeostatic maintenance of the neuronal activity.
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration and Repair, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Yan
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Christoph
authors.initials: C
authors.lastname: Straub
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Susumu
authors.initials: S
authors.lastname: Tomita
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000502:physiology; D005071:Evoked Potentials / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D020239:Receptor Cross-Talk / Q000502:physiology; D018091:Receptors, AMPA / Q000172:deficiency* / Q000502:physiology; D017470:Receptors, Glutamate / Q000145:classification / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D015398:Signal Transduction; D055366:Synaptic Potentials / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate