Selective block of postsynaptic kainate receptors reveals their function at hippocampal mossy fiber synapses

Cerebral Cortex
Paulo S PinheiroChristophe Mulle

Abstract

Progress in understanding the roles of kainate receptors (KARs) in synaptic integration, synaptic networks, and higher brain function has been hampered by the lack of selective pharmacological tools. We have found that UBP310 and related willardiine derivatives, previously characterized as selective GluK1 and GluK3 KAR antagonists, block postsynaptic KARs at hippocampal mossy fiber (MF) CA3 synapses while sparing AMPA and NMDA receptors. We further show that UBP310 is an antagonist of recombinant GluK2/GluK5 receptors, the major population of KARs in the brain. Postsynaptic KAR receptor blockade at MF synapses significantly reduces the sustained depolarization, which builds up during repetitive activity, and impacts on spike transmission mediated by heterosynaptic signals. In addition, KARs present in aberrant MF synapses in the epileptic hippocampus were also blocked by UBP310. Our results support a specific role for postsynaptic KARs in synaptic integration of CA3 pyramidal cells and describe a tool that will be instrumental in understanding the physiopathological role of KARs in the brain.

References

Jun 1, 1986·Journal of Neurophysiology·B Lancaster, P R Adams
Mar 1, 1972·Electroencephalography and Clinical Neurophysiology·R J Racine
Jul 10, 1997·Nature·M Vignes, G L Collingridge
Apr 10, 1999·Nature Neuroscience·M FrerkingR A Nicoll
Feb 16, 2005·Transcultural Psychiatry·Phyllis ZelkowitzJoelle Dayan
Sep 9, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jérôme EpszteinValérie Crépel
Dec 16, 2005·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Arnaud RuizChristophe Mulle
Mar 17, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Mark L MayerDavid E Jane
Jul 19, 2006·Cell and Tissue Research·Paulo Pinheiro, Christophe Mulle
Oct 28, 2006·The Journal of Physiology·Ellen J YangDiana L Pettit
Mar 3, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·John R HuxterRobert U Muller
Jul 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Paulo S PinheiroChristophe Mulle
Sep 4, 2007·Progress in Brain Research·F Edward Dudek, Thomas P Sutula
Sep 7, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Miri GoldinRosa Cossart
May 10, 2008·Nature Reviews. Neuroscience·Paulo S Pinheiro, Christophe Mulle
Jun 20, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Andrea BarberisChristophe Mulle
Sep 2, 2008·Neuropharmacology·David PerraisChristophe Mulle
Sep 17, 2008·Neuropharmacology·David E JaneGraham L Collingridge
Dec 27, 2008·Neuron·Hyung-Bae Kwon, Pablo E Castillo
Jan 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Joyce Wondolowski, Matthew Frerking
Apr 17, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Shankar SachidhanandamChristophe Mulle
Dec 23, 2009·The Journal of Physiology·David D MottMorris Benveniste
May 20, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bryan A CopitsGeoffrey T Swanson
Jul 29, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Julien ArtinianValérie Crépel
Nov 25, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Janet L Fisher, David D Mott

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Citations

Sep 6, 2012·Nature Reviews. Neuroscience·Bryan A Copits, Geoffrey T Swanson
Feb 25, 2014·Nature Chemical Biology·Andreas Reiner, Ehud Y Isacoff
Jan 29, 2016·Journal of Epilepsy Research·L K FriedmanS S Ali
Jan 10, 2016·Neuroscience Research·Etsuko Suzuki, Haruyuki Kamiya
Apr 18, 2014·The European Journal of Neuroscience·Mario CartaChristophe Mulle
Jan 15, 2015·Annals of Neurology·Julien ArtinianValérie Crépel
Oct 22, 2013·Neuron·Juan Lerma, Joana M Marques
Dec 17, 2014·Current Opinion in Pharmacology·Valérie Crépel, Christophe Mulle
Feb 14, 2017·Nature Neuroscience·Milos M PetrovicJeremy M Henley
Mar 3, 2017·Nature Reviews. Neuroscience·Nelson RebolaChristophe Mulle
Nov 29, 2017·Frontiers in Neural Circuits·Lim-Anna SieuIvan Cohen
Dec 21, 2018·The Journal of Physiology·Danielle GarandMelanie A Woodin
Jan 8, 2014·The Journal of Physiology·Sarah H LindstromSteven H DeVries
Mar 13, 2020·The Journal of Physiology·Jessica C Pressey, Melanie A Woodin
Jul 11, 2018·Frontiers in Molecular Neuroscience·Rafael Falcón-MoyaAntonio Rodríguez-Moreno
Oct 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Stefan Pollok, Andreas Reiner
Feb 22, 2017·Scientific Reports·Christopher G DenglerDouglas A Coulter
May 8, 2018·Scientific Reports·Denise K GrosenbaughSantina A Zanelli
Apr 30, 2021·Neuropharmacology·Jeremy M HenleyKevin A Wilkinson
Apr 29, 2021·Neuropharmacology·Sari E LauriTomi Taira
Jun 29, 2021·Revue neurologique·T Marissal
Jul 12, 2021·Neuropharmacology·Christophe Mulle, Valérie Crépel
Sep 24, 2021·Nature·Lingli HeYan Zhao
Sep 30, 2021·The Journal of Physiology·Niccolò P Pampaloni, Andrew J R Plested

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