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Neuron–glia communication contributes to the fine-tuning of synaptic functions. Oligodendrocytes near synapses detect and respond to neuronal activity, but their role in synapse development and plasticity remains largely unexplored. We show that oligodendrocytes modulate neurotransmitter release at presynaptic terminals through secretion of brain-derived neurotrophic factor (BDNF). Oligodendrocyte-derived BDNF functions via presynaptic tropomyosin receptor kinase B (TrkB) to ensure fast, reliable neurotransmitter release and auditory transmission in the developing brain. In auditory brainstem slices from  Bdnf  +/–  mice, reduction in endogenous BDNF significantly decreased vesicular glutamate release by reducing the readily releasable pool of glutamate vesicles, without altering presynaptic Ca 2+  channel activation or release probability. Using conditional knockout mice, cell-specific ablation of BDNF in oligodendrocytes largely recapitulated this effect, which was recovered by BDNF or TrkB agonist application. This study highlights a novel function for oligodendrocytes in synaptic transmission and their potential role in the activity-dependent refinement of presynaptic properties.

Oligodendrocytes regulate presynaptic properties and neurotransmission through BDNF signaling in the mouse brainstem