Cornichon2 dictates the time course of excitatory transmission at individual hippocampal synapses.
Cornichon2 (CNIH2), an integral component of AMPA receptor (AMPAR) complexes in the mammalian brain, slows deactivation and desensitization of heterologously reconstituted receptor channels. Its significance in neuronal signal transduction, however, has remained elusive. Here we show by paired recordings that CNIH2-containing AMPARs dictate the slow decay of excitatory postsynaptic currents (EPSCs) elicited in hilar mossy cells of the hippocampus by single action potentials in mossy fiber boutons (MFB). Selective knockdown of CNIH2 markedly accelerated EPSCs in individual MFB-mossy cell synapses without altering the EPSC amplitude. In contrast, the rapidly decaying EPSCs in synapses between MFBs and aspiny interneurons that lack expression of CNIH2 were unaffected by the protein knockdown but were slowed by virus-directed expression of CNIH2. These results identify CNIH2 as the molecular distinction between slow and fast EPSC phenotypes and show that CNIH2 influences the time course and, hence, the efficacy of excitatory synaptic transmission.
Institute of Physiology, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
Sami
S
Boudkkazi
Institute of Physiology, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
Aline
A
Brechet
Institute of Physiology, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Center for Biological Signalling Studies (BIOSS), Albertstr. 10, 79104 Freiburg, Germany.
Jochen
J
Schwenk
Institute of Physiology, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany; Center for Biological Signalling Studies (BIOSS), Albertstr. 10, 79104 Freiburg, Germany. Electronic address: bernd.fakler@physiologie.uni-freiburg.de.
Bernd
B
Fakler
D000818:Animals; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D005786:Gene Expression Regulation / Q000235:genetics; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology*; D013997:Time Factors; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
D018091:Receptors, AMPA; C539313:Cnih2 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C104722:glutamate receptor ionotropic, AMPA 2