title: Reactive oxygen species mediate activity-dependent neuron-glia signaling in output fibers of the hippocampus.
abstract: Nonsynaptic signaling is becoming increasingly appreciated in studies of activity-dependent changes in the nervous system. We investigated the types of neuronal activity that elicit nonsynaptic communication between neurons and glial cells in hippocampal output fibers. High-frequency, but not low-frequency, action potential firing in myelinated CA1 axons of the hippocampus resulted in increased phosphorylation of the oligodendrocyte-specific protein myelin basic protein (MBP). This change was blocked by tetrodotoxin, indicating that axonally generated action potentials were necessary to regulate the phosphorylation state of MBP. Furthermore, scavengers of the reactive oxygen species superoxide and hydrogen peroxide and nitric oxide synthase inhibitors prevented activation of this neuron-glia signaling pathway. These results indicate that, during periods of increased neuronal activity in area CA1 of the hippocampus, reactive oxygen and nitrogen species are generated, which diffuse to neighboring oligodendrocytes and result in post-translational modifications of MBP, a key structural protein in myelin. Thus, in addition to their well-known capacity for activity-dependent neuron-neuron signaling, hippocampal pyramidal neurons possess a mechanism for activity-dependent neuron-glia signaling.
authors.affiliation: Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: C M
authors.initials: CM
authors.lastname: Atkins
authors.forename: J D
authors.initials: JD
authors.lastname: Sweatt
mesh_terms: D000200:Action Potentials; D000818:Animals; D001369:Axons / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D004558:Electric Stimulation; D006624:Hippocampus / Q000502:physiology*; D066298:In Vitro Techniques; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000502:physiology*; D009457:Neuroglia / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology; D011712:Pyramidal Tracts / Q000502:physiology; D017382:Reactive Oxygen Species / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D004676:Myelin Basic Protein; D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D002374:Catalase; D013482:Superoxide Dismutase; D011493:Protein Kinase C