Interneurons and oligodendrocyte progenitors form a structured synaptic network in the developing neocortex

Abstract

NG2 cells, oligodendrocyte progenitors, receive a major synaptic input from interneurons in the developing neocortex. It is presumed that these precursors integrate cortical networks where they act as sensors of neuronal activity. We show that NG2 cells of the developing somatosensory cortex form a transient and structured synaptic network with interneurons that follows its own rules of connectivity. Fast-spiking interneurons, highly connected to NG2 cells, target proximal subcellular domains containing GABAA receptors with γ2 subunits. Conversely, non-fast-spiking interneurons, poorly connected with these progenitors, target distal sites lacking this subunit. In the network, interneuron-NG2 cell connectivity maps exhibit a local spatial arrangement reflecting innervation only by the nearest interneurons. This microcircuit architecture shows a connectivity peak at PN10, coinciding with a switch to massive oligodendrocyte differentiation. Hence, GABAergic innervation of NG2 cells is temporally and spatially regulated from the subcellular to the network level in coordination with the onset of oligodendrogenesis.DOI: http://dx.doi.org/10.7554/eLife.06953.001

Cognitive deficits in mice lacking Nsun5, a cytosine‐5 RNA methyltransferase, with impairment of oligodendrocyte precursor cells

“…One interesting observation in this study is that the level of GluA2 was lower in Nsun5-KO mice. NG2+ OPCs in the developing somatosensory cortex form a transient and structured synaptic network with interneurons that follows its own rules of connectivity (Orduz et al, 2015). The activation of Ca 2+ -permeable AMPAr has been demonstrated to be important for the proliferation of NG2+ OPCs (Zonouzi, Renzi, Farrant, & Cull-Candy, 2011).…”

Wrapped to Adapt: Experience-Dependent Myelination

“…While this signaling was originally thought to arise from tonic activation as reported in other glia (Bergles et al, 2010), the discovery that OPCs form bona fide synapses in the central nervous system stimulated great interest in synaptic communication as a potential regulator of adaptive myelination (Bergles et al, 2000). Both glutamatergic (Bergles et al, 2000; De Biase et al, 2010; Karadottir et al, 2008; Kukley et al, 2010; Mangin et al, 2008; Ziskin et al, 2007; Zonouzi et al, 2011) and GABAergic (Lin and Bergles, 2004a; Orduz et al, 2015; Velez-Fort et al, 2010) synaptic inputs to OPCs have been identified, the properties of which have been reviewed in detail (Bergles et al, 2010). These observations underlie a compelling hypothesis that neuron-OPC synaptic activity might guide patterns of adaptive myelination.…”

A specific GABAergic synapse onto oligodendrocyte precursors does not regulate cortical oligodendrogenesis

“…In the somatosensory cortex, fast GABAergic synaptic transmission onto OPCs is transient with a connectivity peak at postnatal day 10 (P10) correlated with the onset of oligodendrogenesis (Orduz et al, ; Vélez‐Fort, Maldonado, Butt, Audinat, & Angulo, ). This transient innervation is concomitant to the temporal expression window of the γ2 subunit of GABA A receptors (γ2‐GABA A Rs) in OPCs (Balia et al, ), a subunit preferentially expressed at unitary synaptic connections between parvalbumin (PV)‐expressing fast‐spiking interneurons and OPCs (Orduz et al, ). Along the oligodendrocyte lineage, γ2 expression is restricted to the OPC stage (Zhang et al, ; Arellano et al, ) and γ2‐GABA A Rs are exclusively located at OPC postsynaptic sites (Balia et al, ; Orduz et al, ; Passlick et al, ).…”