OLIGODENDROGLIAL SIGNAL-TRANSDUCTION SYSTEMS ARE REGULATED BY NEURONAL CONTACT

Previous reports indicate that oligodendrocytes express signaling syst ems activated by classical neurotransmitters. Several signaling system s linked to mobilization of intracellular calcium have been demonstrat ed, and some of these are developmentally lost in vitro and in vivo. T he experiments described here use oligodendrocyte-neuron cocultures to examine the effects of neuronal contact on the expression of these si gnaling pathways, Neonatal rat cerebral oligodendrocytes in contact wi th dorsal root ganglia (DRG) neurites responded to bath application of histamine, ATP, carbachol, glutamate, or bradykinin with increases in intracellular Ca2+ concentration. Similar results were obtained in co culture with superior cervical ganglia neurons. Preventing neuronal co ntact by transection of DRG neurites significantly reduced the percent age of oligodendrocytes responsive to each ligand, with the exception of bradykinin responsiveness, which was unaffected. Oligodendroglia is olated from adult rat spinal cord were also examined for responsivenes s to these neuroligands. Few isolated adult oligodendroglia were respo nsive to these ligands, and coculture with DRG neurons failed to resto re responsiveness. Neuroligand responsiveness was not induced in oligo dendrocytes maintained 8 days in purified culture before establishment of cocultures. A significant reduction in the number of neuroligand-r esponsive oligodendroglia was noted for histamine, carbachol, glutamat e, and ATP after including tetrodotoxin for the final 6 days of cocult ure. These results suggest that both neuronal contact and neuronal act ivity contribute to the maintenance of functional neurotransmitter-act ivated signaling pathways coupled to mobilization of intracellular cal cium in oligodendrocytes.