Postnatal down-regulation of the GABAA receptor γ2 subunit in neocortical NG2 cells accompanies synaptic-to-extrasynaptic switch in the GABAergic transmission mode.
Cerebral Cortex. 2013-11-11; 25(4): 1114-1123
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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.