Neuronal input triggers Ca2+ influx through AMPA receptors and voltage-gated Ca2+ channels in oligodendrocytes

Communication between neurons and developing oligodendrocytes (OLs) leading to OL Ca²⁺ rise is critical for axon myelination and OL development. Here, we investigate signaling factors and sources of Ca²⁺ rise in OLs in the mouse brainstem. Glutamate puff or axon fiber stimulation induces a Ca²⁺ rise in pre-myelinating OLs, which is primarily mediated by Ca²⁺-permeable AMPA receptors. During glutamate application, inward currents via AMPA receptors and elevated extracellular K⁺ caused by increased neuronal activity collectively lead to OL depolarization, triggering Ca²⁺ influx via P/Q- and L-type voltage-gated Ca²⁺ (Ca_v) channels. Thus, glutamate is a key signaling factor in dynamic communication between neurons and OLs that triggers Ca²⁺ transients via AMPARs and Ca_v channels in developing OLs. The results provide a mechanism for OL Ca²⁺ dynamics in response to neuronal input, which has implications for OL development and myelination.