Glia as transmitter sources and sensors in health and disease

Glial cells express a bewildering array of neurotransmitter receptors. To illustrate the complexity of expression, we have assayed non-glutamatergic neurotransmitter receptor mRNA in isolated rat optic nerve, a preparation devoid of neurons and neuronal synapses and from which relatively pure “glial” RNA can be isolated. Of the 44 receptor subunits examined which span the GABA-A, nicotinic, adreno- and glycine receptor families, over three quarters were robustly expressed in this mixed population of white matter glial cells, with several expressed at higher levels than found in control whole brain RNA. In addition to the complexity of glial receptor expression, numerous neurotransmitter release mechanisms have been identified. We have focused on glutamate release from astrocytes, which can occur via at least seven distinct pathways and which is implicated in excitotoxic injury and are neurons and glia. Recent findings suggest that non-glutamatergic receptors can also mediate acute glial injury are also discussed.