Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus

Fast excitatory neurotransmission in the central nervous system occurs at s pecialized synaptic junctions between neurons, where a high concentration o f glutamate directly activates receptor channels. Low-affinity AMPA (alpha- amino-3-hydroxy-5-methyl isoxazole propionic acid) and kainate glutamate re ceptors are also expressed by some glial cells(1), including oligodendrocyt e precursor cells (OPCs). However, the conditions that result in activation of glutamate receptors on these non-neuronal cells are not known. Here we report that stimulation of excitatory axons in the hippocampus elicits inwa rd currents in OPCs that are mediated by AMPA receptors. The quantal nature of these responses and their rapid kinetics indicate that they are produce d by the exocytosis of vesicles filled with glutamate directly opposite the se receptors. Some of these AMPA receptors are permeable to calcium ions, p roviding a link between axonal activity and internal calcium levels in OPCs . Electron microscopic analysis revealed that vesicle-filled axon terminals make synaptic junctions with the processes of OPCs in both the young and a dult hippocampus. These results demonstrate the existence of a rapid signal ling pathway from pyramidal neurons to OPCs in the mammalian hippocampus th at is mediated by excitatory, glutamatergic synapses.