Axon‐glia communication evokes calcium signaling in olfactory ensheathing cells of the developing olfactory bulb

Abstract

Olfactory ensheathing cells (OECs) accompany receptor axons in the olfactory nerve and promote axonal growth into the central nervous system. The mechanisms underlying the communication between axons and OECs, however, have not been studied in detail yet. We investigated the effect of activity-dependent neuronal transmitter release on Ca²⁺ signaling of OECs in acute mouse olfactory bulb slices using confocal Ca²⁺ imaging. TTX-sensitive axonal activity upon electrical nerve stimulation triggers a rise in cytosolic Ca²⁺ in OECs, which can be mimicked by application of DHPG, an agonist of metabotropic glutamate receptors (mGluRs). Both stimulation- and DHPG-induced Ca²⁺ transients in OECs were abolished by depletion of intracellular Ca²⁺ stores with cyclopiazonic acid (CPA). The mGluR₁-specific antagonist CPCCOEt completely inhibited DHPG-evoked Ca²⁺ transients, but reduced stimulation-induced Ca²⁺ transients only partly, suggesting the involvement of another neurotransmitter. Application of ATP evoked CPA-sensitive Ca²⁺ transients in OECs, which were inhibited by the P2Y₁-specific antagonist MRS2179. Co-application of CPCCOEt and MRS2179 almost completely blocked the stimulation-induced Ca²⁺ transients, indicating that they were mediated by mGluR₁ and P2Y₁ receptors. Our results show that OECs are able to respond to olfactory nerve activity with an increase in cytosolic Ca²⁺ due to glutamate and ATP release.