Functional ionotropic glutamate receptors on peripheral axons and myelin

Introduction: Neurotransmitter-dependent signaling is traditionally restricted to axon terminals. However, receptors are present on myelinating glia, suggesting that chemical transmission may also occur along axons. Methods: Confocal microscopy and Ca2+-imaging using an axonally expressed FRET-based reporter was used to measure Ca2+ changes and morphological alterations in myelin in response to stimulation of glutamate receptors. Results: Activation of -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) or N-methyl-D-aspartate (NMDA) receptors induced a Ca2+ increase in axon cylinders. However, only the latter caused structural alterations in axons, despite similar Ca2+ increases. Myelin morphology was significantly altered by NMDA receptor activation, but not by AMPA receptors. Cu2+ ions influenced the NMDA receptor-dependent response, suggesting that this metal modulates axonal receptors. Glutamate increased ribosomal signal in Schwann cell cytoplasm. Conclusions: Axon cylinders and myelin of peripheral nervous system axons respond to glutamate, with a consequence being an increase in Schwann cell ribosomes. This may have implications for nerve pathology and regeneration. Muscle Nerve54: 451-459, 2016