Postnatal down-regulation of the GABAA receptor γ2 subunit in neocortical NG2 cells accompanies synaptic-to-extrasynaptic switch in the GABAergic transmission mode.
NG2 cells, a main pool of glial progenitors, express γ-aminobutyric acid A (GABA(A)) receptors (GABA(A)Rs), the functional and molecular properties of which are largely unknown. We recently reported that transmission between GABAergic interneurons and NG2 cells drastically changes during development of the somatosensory cortex, switching from synaptic to extrasynaptic communication. Since synaptic and extrasynaptic GABA(A)Rs of neurons differ in their subunit composition, we hypothesize that GABA(A)Rs of NG2 cells undergo molecular changes during cortical development accompanying the switch of transmission modes. Single-cell RT-PCR and the effects of zolpidem and α5IA on evoked GABAergic currents reveal the predominance of functional α1- and α5-containing GABA(A)Rs at interneuron-NG2 cell synapses in the second postnatal week, while the α5 expression declines later in development when responses are exclusively extrasynaptic. Importantly, pharmacological and molecular analyses demonstrate that γ2, a subunit contributing to the clustering of GABA(A)Rs at postsynaptic sites in neurons, is down-regulated in NG2 cells in a cell type-specific manner in concomitance with the decline of synaptic activity and the switch of transmission mode. In keeping with the synaptic nature of γ2 in neurons, the down-regulation of this subunit is an important molecular hallmark of the change of transmission modes between interneurons and NG2 cells during development.
INSERM U603, Paris, France CNRS UMR 8154, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France and.
Maddalena
M
Balia
INSERM U603, Paris, France CNRS UMR 8154, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France and Current address: Division of Neurophysiology, The National Institute for Medical Research, Mill Hill NW7 1AA, UK.
Mateo
M
Vélez-Fort
Institute of Cellular Neurosciences, University of Bonn, Bonn 53105, Germany.
Stefan
S
Passlick
Institute of Cellular Neurosciences, University of Bonn, Bonn 53105, Germany Current address: Institute of Neurophysiology, University of Cologne, 50931 Cologne, Germany.
Christoph
C
Schäfer
INSERM U603, Paris, France CNRS UMR 8154, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France and.
Etienne
E
Audinat
Institute of Cellular Neurosciences, University of Bonn, Bonn 53105, Germany.
Christian
C
Steinhäuser
Institute of Cellular Neurosciences, University of Bonn, Bonn 53105, Germany.
Gerald
G
Seifert
INSERM U603, Paris, France CNRS UMR 8154, Paris, France Université Paris Descartes, Sorbonne Paris Cité, Paris, France and.
María Cecilia
MC
Angulo
D000818:Animals; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation; D004558:Electric Stimulation; D058785:GABA-A Receptor Agonists / Q000494:pharmacology; D007395:Interneurons / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008822:Mice, Transgenic; D019579:Neocortex / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism*; D059010:Single-Cell Analysis; D013003:Somatosensory Cortex / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D000077334:Zolpidem; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D058785:GABA-A Receptor Agonists; C496250:Gabra5 protein, mouse; C546280:Gabrg2 protein, mouse; D011725:Pyridines; D012333:RNA, Messenger; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D000077334:Zolpidem
GABA spillover; GABAA receptor γ2 subunit; oligodendrocyte precursor cell; single-cell RT–PCR; synaptic transmission