Effects of visual deprivation on remodeling of nodes of Ranvier in optic nerve

Abstract

Oligodendrocytes, the myelinating cell of the central nervous system (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 if 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 P40-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.

Significance Statement

Recent studies show that nodes of Ranvier can undergo activity-dependent remodeling, but the mechanisms are unclear. Indeed, whether sensory deprivation alters nodes of Ranvier has not been tested. An implicit assumption in studies of sensory experience on synaptic plasticity, e.g., the classical Hubel and Wiesel studies and others, is that binocular visual deprivation (BVD) does not change myelin to alter action potential conduction. Here, we test that assumption and also determine the effect of BVD on a specific astrocyte-mediated mechanism of node of Ranvier plasticity in optic nerve of adult mice. The astrocyte-mediated nodal gap lengthening proceeded normally in adult mice maintained in the dark for 30 days. Secondly, the absence of plasticity of nodes of Ranvier in controls parallels our understanding of synaptic plasticity in visual cortex following BVD.