title: Target-specific expression of presynaptic NMDA receptors in neocortical microcircuits.
abstract: Traditionally, NMDA receptors are located postsynaptically; yet, putatively presynaptic NMDA receptors (preNMDARs) have been reported. Although implicated in controlling synaptic plasticity, their function is not well understood and their expression patterns are debated. We demonstrate that, in layer 5 of developing mouse visual cortex, preNMDARs specifically control synaptic transmission at pyramidal cell inputs to other pyramidal cells and to Martinotti cells, while leaving those to basket cells unaffected. We also reveal a type of interneuron that mediates ascending inhibition. In agreement with synapse-specific expression, we find preNMDAR-mediated calcium signals in a subset of pyramidal cell terminals. A tuned network model predicts that preNMDARs specifically reroute information flow in local circuits during high-frequency firing, in particular by impacting frequency-dependent disynaptic inhibition mediated by Martinotti cells, a finding that we experimentally verify. We conclude that postsynaptic cell type determines presynaptic terminal molecular identity and that preNMDARs govern information processing in neocortical columns.
authors.affiliation: Department of Neuroscience, Physiology, and Pharmacology, University College London, 21 University Street, London WC1E 6DE, UK.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Buchanan
authors.forename: Arne V
authors.initials: AV
authors.lastname: Blackman
authors.forename: Alexandre W
authors.initials: AW
authors.lastname: Moreau
authors.forename: Dale
authors.initials: D
authors.lastname: Elgar
authors.forename: Rui P
authors.initials: RP
authors.lastname: Costa
authors.forename: Txomin
authors.initials: T
authors.lastname: Lalanne
authors.forename: Adam A
authors.initials: AA
authors.lastname: Tudor Jones
authors.forename: Julia
authors.initials: J
authors.lastname: Oyrer
authors.forename: P Jesper
authors.initials: PJ
authors.lastname: Sjöström
mesh_terms: D000818:Animals; D003198:Computer Simulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D019579:Neocortex / Q000166:cytology / Q000378:metabolism*; D009434:Neural Pathways / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate