title: Synapse-specific expression of calcium-permeable AMPA receptors in neocortical layer 5.
abstract: CONCLUSIONS
  In the hippocampus, calcium-permeable AMPA receptors have been found in a restricted subset of neuronal types that inhibit other neurons, although their localization in the neocortex is less well understood. In the present study, we looked for calcium-permeable AMPA receptors in two distinct populations of neocortical inhibitory neurons: basket cells and Martinotti cells. We found them in the former but not in the latter. Furthermore, in basket cells, these receptors were associated with particularly fast responses. Computer modelling predicted (and experiments verified) that fast calcium-permeable AMPA receptors enable basket cells to respond rapidly, such that they promptly inhibit neighbouring cells and shut down activity. The results obtained in the present study help our understanding of pathologies such as stroke and epilepsy that have been associated with disordered regulation of calcium-permeable AMPA receptors.
  AMPA-type glutamate receptors (AMPARs) lacking an edited GluA2 subunit are calcium-permeable (CP) and contribute to synaptic plasticity in several hippocampal interneuron types, although their precise role in the neocortex is not well described. We explored the presence of CP-AMPARs at pyramidal cell (PC) inputs to Martinotti cells (MCs) and basket cells (BCs) in layer 5 of the developing mouse visual cortex (postnatal days 12-21). GluA2 immunolabelling was stronger in MCs than in BCs. A differential presence of CP-AMPARs at PC-BC and PC-MC synapses was confirmed electrophysiologically, based on measures of spermine-dependent rectification and CP-AMPAR blockade by 1-naphtyl acetyl spermine using recordings from synaptically connected cell pairs, NPEC-AMPA uncaging and miniature current recordings. In addition, CP-AMPAR expression in BCs was correlated with rapidly decaying synaptic currents. Computer modelling predicted that this reduces spike latencies and sharpens suprathreshold responses in BCs, which we verified experimentally using the dynamic clamp technique. Thus, the synapse-specific expression of CP-AMPARs may critically influence both plasticity and information processing in neocortical microcircuits.
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.|Integrated Program in Neuroscience, McGill University, Montreal, Quebec, Canada.
authors.forename: Txomin
authors.initials: T
authors.lastname: Lalanne
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Julia
authors.initials: J
authors.lastname: Oyrer
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Adamo
authors.initials: A
authors.lastname: Mancino
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Erica
authors.initials: E
authors.lastname: Gregor
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Chung
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Louis
authors.initials: L
authors.lastname: Huynh
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Sasha
authors.initials: S
authors.lastname: Burwell
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Maheux
authors.affiliation: Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Farrant
authors.affiliation: Centre for Research in Neuroscience, Department of Neurology and Neurosurgery, The Research Institute of the McGill University Health Centre, Montreal General Hospital, Montreal, Quebec, Canada.|Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
authors.forename: P Jesper
authors.initials: PJ
authors.lastname: Sjöström
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D019579:Neocortex / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000502:physiology; D055366:Synaptic Potentials
chemical_list: D018091:Receptors, AMPA; D002118:Calcium