NEUROTRANSMITTER-MEDIATED SIGNALING BETWEEN AXONS AND GLIAL-CELLS

Neurotransmitter-mediated signaling is not restricted to the synaptic regions of the nervous system but also takes places along fiber tracts lacking vesicular means of releasing neuroactive substances. The firs t demonstration for dynamic signaling of this type came in the early 1 970s from studies by Villegas and co-workers in squid axons and their satellite Schwann cells. In this invertebrate system, glutamate has be en identified as the mediator of this signaling in being first release d from the active axons thus setting off a series of cascades, leading to a cholinergic activation of the Schwann cell membrane. Recent evid ence suggests that receptor-mediated signaling also exists between gli al cells and axons in vertebrates. In the frog optic nerve, axonal act ivity facilitated the activity of glial ion channels. In the neonatal rat optic nerve, electrical activity of axons triggered oscillations i n intracellular calcium in a subset of glial cells. These observations have been postulated to reflect receptor-mediated signaling, includin g a mechanism in which glutamate is released from axons via the revers al of a transporter and induces intracellular calcium spiking in glial cells via metabotropic glutamate receptors. The efficacy of ''axon-to -glia'' transmission may, like that in ''neuron-to-neuron'' transmissi on, be modulated by co-release of multiple neuroactive substances. One possibility is that adenosine, which is known to be released from fib er tracts, can modulate glutamate signaling in white matter by modulat ing the periaxonal glutamate concentration through an effect on the gl ial glutamate uptake system. (C) 1994 Wiley-Liss, Inc.