title: Long-term depression of synaptic kainate receptors reduces excitability by relieving inhibition of the slow afterhyperpolarization.
abstract: Kainate receptors (KARs) are ionotropic glutamate receptors that also activate noncanonical G-protein-coupled signaling pathways to depress the slow afterhyperpolarization (sAHP). Here we show that long-term depression of KAR-mediated synaptic transmission (KAR LTD) at rat hippocampal mossy fiber synapses relieves inhibition of the sAHP by synaptic transmission. KAR LTD is induced by high-frequency mossy fiber stimulation and natural spike patterns and requires activation of adenosine A2A receptors. Natural spike patterns also cause long-term potentiation of NMDA receptor-mediated synaptic transmission that overrides the effects of KAR LTD on the cellular response to low-frequency synaptic input. However, KAR LTD is dominant at higher frequency synaptic stimulation where it decreases the cellular response by relieving inhibition of the sAHP. Thus we describe a form of glutamate receptor plasticity induced by natural spike patterns whose primary physiological function is to regulate cellular excitability.
authors.affiliation: MRC Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, University Walk, Bristol, BS8 1TD, United Kingdom.
authors.forename: Sophie E L
authors.initials: SE
authors.lastname: Chamberlain
authors.forename: Josef H L P
authors.initials: JH
authors.lastname: Sadowski
authors.forename: Leonor M
authors.initials: LM
authors.lastname: Teles-Grilo Ruivo
authors.forename: Laura A
authors.initials: LA
authors.lastname: Atherton
authors.forename: Jack R
authors.initials: JR
authors.lastname: Mellor
mesh_terms: D000818:Animals; D056654:CA3 Region, Hippocampal / Q000166:cytology / Q000502:physiology; D003627:Data Interpretation, Statistical; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A / Q000502:physiology; D018092:Kainic Acid Receptors / Q000187:drug effects / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D043705:Receptor, Adenosine A2A; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate