RESUMEN
Oligodendrocytes, the myelinating cells of the CNS, promote rapid action potential conduction along axons. Changes in the geometry of gaps between myelin segments, known as nodes of Ranvier, affect the conduction speed of neuronal impulses and can ultimately alter neural synchronization and circuit function. In contrast to synaptic plasticity, much less is known about how neural activity may affect node of Ranvier structure. Recently, perinodal astrocytes have been shown to remodel nodes of Ranvier by regulating thrombin proteolysis, but it is not known whether neural activity influences this process. To test this hypothesis, we used transgenic mice with astrocytic expression of a dominant-negative vesicle-associated membrane protein 2 ([gfap]dnVAMP2) to reduce exocytosis of thrombin inhibitors, modulating astrocytic regulation of paranodal loop attachment to induce nodal remodeling, under normal conditions and in adult mice maintained in darkness from postnatal day 40 (P40) to P70. This mechanism of nodal lengthening proceeded normally following binocular visual deprivation (BVD). The effect of BVD on nodal plasticity in animals with unimpaired astrocyte function has not been previously investigated. We find that when exocytosis from astrocytes was unimpaired, nodal gap length was not altered by BVD in adult mice. We conclude that if perinodal astrocytes participate in activity-dependent myelin remodeling through exocytosis, then, as with synaptic plasticity in the visual system, the process must be driven by alterations in neuronal firing other than those produced by BVD.
Asunto(s)
Nódulos de Ranvier , Trombina , Ratones , Animales , Nódulos de Ranvier/metabolismo , Trombina/metabolismo , Nervio Óptico , Vaina de Mielina/metabolismo , Axones , Ratones TransgénicosRESUMEN
Interactions between microglia, the resident macrophages of the central nervous system (CNS), and myelin, the glial sheath on nerve fibers essential for rapid neural impulse transmission, are commonly studied in the context of neurotrauma and disease. However, interactions between microglia and myelin under normal physiological conditions have been largely overlooked. This review summarizes recent research indicating that the unique properties of microglia evident in disease states also enable microglia to regulate myelination during development and throughout life. This includes phagocytosis of cells and myelin membrane as well as the release of trophic factors, cytokines, and chemokines. The ability of microglia to sense neuronal activity and molecular features of the microenvironment enables them to optimize myelination by influencing early oligodendrogenesis, myelin formation, and removal of aberrantly targeted myelin. Understanding how microglia participate in myelination under normal conditions provides a new perspective that will increase understanding of developmental abnormalities.