Neurotransmitter-mediated axon-glia communication in the central and peripheral nervous system.
University of Tübingen, Germany
Oligodendrocyte precursors cells (OPCs) are the glial cells of the central nervous system which give rise to myelinating oligodendrocytes during development and in the adult brain, and hence play an important role in establishing and maintaining the healthy function of the nervous system. A few years ago, we discovered that axons in white matter areas of rodent and human brain are involved in glutamatergic synaptic signalling with OPCs. At these neuron-glia synapses, action potentials trigger a fast vesicular release of the neurotransmitter glutamate which binds to ionotropic glutamate receptors (AMPA receptors) on the OPCs and leads to the activation of a depolarizing current. The functional role of axon-OPC synapses currently remains a puzzle. Remarkably, a leading concept in the field states that proliferation and differentiation of OPCs, as well as myelination, are influenced by neuronal activity. As neuron-OPC synapses represent the points of direct structural and functional interaction between the two cell types, they appear to be ideal sites at which the effects of neuronal activity can be conveyed to glial cells. To test this idea, in our recent work we transiently modified the properties of AMPA receptors at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination, by targeting the GluA2 subunit. This resulted in altere proliferation of OPCs and/or their differentiation into oligodendrocytes. Our findings open an exciting possibility that the purpose of synapses in the brain is not restricted to the transmission and propagation of nerve impulses in neuronal networks. Neuron-glia synapses likely have a completely different meaning and might allow neuronal cells to modulate the fate choice and/or self-renewal of glial cells.
Our discovery of synaptic signalling between axons and OPCs in the white matter of the brain and in the optic nerve prompted a question whether similar signalling exists between axons and Schwann cells (or their precursors) in the peripheral nerves. To address this question, we have recently established a novel preparation of the mouse peripheral nerve slices where the connection between axons and Schwann cells should be largely preserved. Using patch-clamp recordings in this preparation, we found that developing Schwann cells in the mouse sciatic nerve express ionotropic glutamate and acetylcholine receptors. Furthermore, using 2-photon Ca2+-imaging, we demonstrated that peripheral axons express functional voltage-gated Ca2+-channels of N- and L-type, and show fastCa2+-transients upon action potential propagation. Supposedly, these Ca2+-channels can mediate fast vesicular neurotransmitter release along the peripheral axons, as it occurs in the CNS white matter. However, we were not able to record spontaneous or evoked synaptic currents in Schwann cells, indicating the neurotransmitter receptors in Schwann cells are activated by a different mechanism.
Further research on neurotransmitter-mediated communication between axons and myelinating glial cells in the central and peripheral nervous system should bring new insights into cell-cell communication during physiological and pathological conditions
Host: Estibaliz Capetillo/Carlos Matute