Short- and long-term functional plasticity of white matter induced by oligodendrocyte depolarization in the hippocampus

• Published in: Glia Vol. 62; no. 8; pp. 1299 - 1312
• Main Authors: Yamazaki, Yoshihiko, Fujiwara, Hiroki, Kaneko, Kenya, Hozumi, Yasukazu, Xu, Ming, Ikenaka, Kazuhiro, Fujii, Satoshi, Tanaka, Kenji F.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01-08-2014; Wiley Subscription Services, Inc
• Subjects: action potential; Action Potentials - drug effects; Animals; Attention Deficit Hyperactivity Disorder; axonal conduction; Axons - drug effects; Axons - physiology; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Brain; channelrhodopsin-2; Channelrhodopsins; Female; Gene expression; Hippocampus - drug effects; Hippocampus - physiology; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Male; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mice, Transgenic; Microelectrodes; Multiple sclerosis; myelin; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Oligodendroglia - drug effects; Oligodendroglia - physiology; Patch-Clamp Techniques; Photic Stimulation; Potassium Channels - metabolism; Pyramidal Cells - drug effects; Pyramidal Cells - physiology; Time Factors; Tissue Culture Techniques; White Matter - drug effects; White Matter - physiology; myelin; action potential; axonal conduction; channelrhodopsin-2
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.22681

Plastic changes in white matter have received considerable attention in relation to normal cognitive function and learning. Oligodendrocytes and myelin, which constitute the white matter in the central nervous system, can respond to neuronal activity with prolonged depolarization of membrane potential and/or an increase in the intracellular Ca2+ concentration. Depolarization of oligodendrocytes increases the conduction velocity of an action potential along axons myelinated by the depolarized oligodendrocytes, indicating that white matter shows functional plasticity, as well as structural plasticity. However, the properties and mechanism of oligodendrocyte depolarization‐induced functional plastic changes in white matter are largely unknown. Here, we investigated the functional plasticity of white matter in the hippocampus using mice with oligodendrocytes expressing channelrhodopsin‐2. Using extracellular recordings of compound action potentials at the alveus of the hippocampus, we demonstrated that light‐evoked depolarization of oligodendrocytes induced early‐ and late‐onset facilitation of axonal conduction that was dependent on the magnitude of oligodendrocyte depolarization; the former lasted for approximately 10 min, whereas the latter continued for up to 3 h. Using whole‐cell recordings from CA1 pyramidal cells and recordings of antidromic action potentials, we found that the early‐onset short‐lasting component included the synchronization of action potentials. Moreover, pharmacological analysis demonstrated that the activation of Ba2+‐sensitive K+ channels was involved in early‐ and late‐onset facilitation, whereas 4‐aminopyridine‐sensitive K+ channels were only involved in the early‐onset component. These results demonstrate that oligodendrocyte depolarization induces short‐ and long‐term functional plastic changes in the white matter of the hippocampus and plays active roles in brain functions. GLIA 2014;62:1299–1312
Main Points
Transcription factor Fosb gene products regulate C5ar1 and C5ar2 gene expression in
microglia.
In the neurodegenerative state, microglial activation was attenuated in Fosb‐null microglia with decreased expression of C5aR1.