Axon-to-Glia Interaction Regulates GABA_AReceptor Expression in Oligodendrocytes

Abstract

Myelination requires oligodendrocyte-neuron communication, and both neurotransmitters and contact interactions are essential for this process. Oligodendrocytes are endowed with neurotransmitter receptors whose expression levels and properties may change during myelination. However, only scant information is available about the extent and timing of these changes or how they are regulated by oligodendrocyte-neuron interactions. Here, we used electrophysiology to study the expression of ionotropic GABA, glutamate, and ATP receptors in oligodendrocytes derived from the optic nerve and forebrain cultured either alone or in the presence of dorsal root ganglion neurons. We observed that oligodendrocytes from both regions responded to these transmitters at 1 day in culture. After the first day in culture, however, GABA sensitivity diminished drastically to less than 10%, while that of glutamate and ATP remained constant. In contrast, the GABA response amplitude was sustained and remained stable in oligodendrocytes cocultured with dorsal root ganglion neurons. Immunochemistry and pharmacological properties of the responses indicated that they were mediated by distinctive GABA A receptors and that in coculture with neurons, the oligodendrocytes bearing the receptors were those in direct contact with axons. These results reveal that GABA A receptor regulation in oligodendrocytes is driven by axonal cues and that GABA signaling may play a role in myelination and/or during axonglia recognition.

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

“…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, ). In this report, we induced a loss‐of‐function of γ2‐GABA A Rs in OPCs to test whether γ2‐mediated synaptic signaling affects OPC dynamics.…”

GAT‐1 mediated GABA uptake in rat oligodendrocytes

“…Although this is the first demonstration that GAT‐1 is expressed in oligodendrocytes, our findings are not surprising given the known relationships between GABA and oligodendrocytes (Hamilton et al, in press; Verkhratsky and Butt, ). Functional GABA A R have been demonstrated in oligodendrocyte progenitor cells (OPCs) and in oligodendrocytes (Arellano et al, ; Berger et al, ; Kirchhoff and Kettenmann, ; Lin and Bergles, ; Vélez‐Fort et al, ; Von Blankenfeld et al, ), and GABAergic synapses from neurons are known to contact OPCs (Lin and Bergles, ; Tanaka et al, ). In addition, GABA B R are expressed by OPCs, and are down‐regulated in myelinating oligodendrocytes (Charles et al, ; Luyt et al, ).…”

Glutamate versus GABA in neuron–oligodendroglia communication

“…Several reports have revealed that the sensitivity to GABA of mature OLs is greatly diminished compared to OPCs, suggesting a specific regulation of GABA A R expression during OL lineage cell development (Figure b; Arellano et al, ; Berger, Walz, Schnitzer, & Kettenmann, ; Von Blankenfeld, Trotter, & Kettenmann, ). Concerning the OL mature state, Arellano et al () recently observed that GABA A R‐mediated responses also drastically decreases with time in isolated OL cultures, while the presence of neurons in cocultures allows for maintaining their functional expression. A direct interaction between neurons and OLs seems therefore necessary to stabilize GABA A Rs in differentiated cells.…”

“…However, the neuron‐to‐OL signals involved in this process remain unknown. Blockade of neuronal activity with the Na + channel blocker TTX does not change OLs sensitivity to GABA, suggesting that a basal neuronal activity is not required to keep GABA A R functional expression (Arellano et al, ).…”