A developmental switch to facilitation shapes synaptic plasticity at neuron-OPC synapses in white matter

Neuronal circuits rely on precisely timed synaptic transmission and plasticity, which are established through activity-dependent maturation during development. While these processes are well characterized at neuronal synapses, far less is known about how synaptic communication between neurons and glial cells develops. Pyramidal cortical neurons project axons through white matter where they release glutamate ectopically along their shafts and form glutamatergic synapses with oligodendrocyte precursor cells (OPCs). The functional maturation of these neuron-glia connections remains unknown. Here, using single-cell electrophysiology combined with computational modelling, we show that neuron-OPC synapses in the mouse corpus callosum undergo a pronounced developmental transformation in short-term synaptic plasticity. During the first two postnatal months, these synapses switch from strong synaptic depression to facilitation. This transition is accompanied by a shortening of synaptic delay and a reduction in asynchronous glutamate release, indicating an increase in temporal precision of neurotransmitter signalling in white matter. Computational modelling suggests that both pre- and postsynaptic changes may underlie this functional maturation. Taken together, our findings demonstrate that neuron-OPC synapses in white matter are not static but undergo developmental transition towards facilitation and temporally precise transmission that parallels the maturation trajectory of classical neuronal synapses in cortical grey matter. These results identify neuron-glia synapses in white matter as dynamic elements of developing neural circuits, and suggest that synaptic release machineries at axonal shafts in white matter and synaptic boutons in grey matter mature in a similar fashion.