Sources of extracellular glutamate in developing white matter

Abstract

Neurotransmitters mediate synaptic communication between neurons and are therefore fundamental to such essential human characteristics as learning, memory, cognition and persona. Recent work indicates that neurotransmitters and their receptors are also used for communication between non-synaptic elements of the nervous system and may be involved in glial-glial, glia-axon and glial-neuronal information transfer and processing. We have recently found evidence that glial cells in developing white matter, which contains no synapses or neuronal somata, express a wide variety of neurotransmitter receptors, including the NMDA-type glutamate receptor that had long thought to be exclusively neuronal. At the point when white matter is laying down myelin and glial cells are forming their long-term morphological arrangement with axons, NMDA receptors mediate post-synaptic-potential input onto glia and may be crucially involved in stabilizing glial-axonal cyto-architecture. There is also strong evidence that glutamate receptors on glial cell membranes greatly heighten the cells susceptibility to injury, a phenomenon that may explain the selective damage of developing white matter found in common human birth disorders such as cerebral palsy. There are many potential sources of extracellular glutamate in ischemic white matter including axons, oligodendrocytes, reverse glutamate transport, loss of astrocyte processes and astrocyte swelling. These potential pathways for glutamate release are described here.