Postnatal Down-Regulation of the GABA(A) Receptor gamma(2) Subunit in Neocortical NG2 Cells Accompanies Synaptic-to-Extrasynaptic Switch in the GABAergic Transmission Mode

作者：Balia Maddalena; Velez Fort Mateo; Passlick Stefan; Schaefer Christoph; Audinat Etienne; Steinhaeuser Christian; Seifert Gerald; Angulo Maria Cecilia^*

来源：Cerebral Cortex, 2015, 25(4): 1114-1123.

DOI：10.1093/cercor/bht309

• GABA spillover
• GABA(A) receptor gamma 2 subunit
• oligodendrocyte precursor cell
• single-cell RT-PCR
• synaptic transmission

NG2 cells, a main pool of glial progenitors, express gamma-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 alpha 5IA on evoked GABAergic currents reveal the predominance of functional alpha 1- and alpha 5-containing GABA(A)Rs at interneuron-NG2 cell synapses in the second postnatal week, while the alpha 5 expression declines later in development when responses are exclusively extrasynaptic. Importantly, pharmacological and molecular analyses demonstrate that gamma(2), 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 gamma(2) 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.

• 出版日期2015-4