Abstract
Purpose :
Monocular and binocular deprivation experiments have established fundamental concepts of synaptic plasticity. Such studies assume that impulses from both eyes are fixed and not influenced by visual experience in adulthood. We hypothesize that monocular deprivation and inhibition result in visual experience-dependent changes in node of Ranvier (NOR) morphology in the visual pathway.
Methods :
We induced monocular inhibition (MI) in retinal ganglion cells of Vglut2CRE mice via overexpression of Kir2.1 (p40-p100; N=6). Additionally, we initiated monocular deprivation (MD) in WT mice by single eye suture (p40-p100; N=3). We isolated optic nerves (ON) and optic tracts (OT) at p100 for immunohistochemistry and quantified NOR gap lengths (NGL). Pattern electroretinogram confirmed that overexpression of Kir2.1 resulted in MI. One-way ANOVA + Tukey-HSD test, Kruskal-Wallis + Dunn’s test, and unpaired Student’s t-tests were used for statistical analysis.
Results :
Following successful MI, NGLs in the inhibited eye ONs were larger on inhibited axons (RFP+) than NGLs on uninhibited (RFP-) axons. NGLs in the uninhibited eye (UE) ONs were larger on RFP+ axons than on RFP- axons from the UE (ANOVA F2, 177 = 35.04, P < 0.0001). Following MI, NGLs were larger on RFP+ axons in the OT contralateral (CL) to the UE (CUE) than RFP- NGLs in the CUE. RFP+ NGLs in the OT ipsilateral (IL) to UE (IUE) were larger than RFP- NGLs in the IUE. RFP+ NGLs in the CUE were larger than RFP- NGLs in the IUE. RFP+ NGLs in the IUE were larger than RFP- NGLs in the CUE. (H(3) = 40.94, P < 0.0001). NGLs were larger in sutured, deprived eyes (MDE) ONs compared to the open eye (OE) ONs following MD (t(66) = 3.240, P = 0.0019). MDE NGLs in the OT CL to OE were larger than MDE NGLs in the OT IL to the OE (IOE). OE NGLs in the IOE were larger than MDE NGLs in the IOE. (H(3) = 12.39, P = 0.0061).
Conclusions :
MD and MI results in activity-dependent changes in NOR morphology of adult mice in the visual pathway, suggesting that axons are dynamically myelinated, demonstrating a previously unsuspected non-synaptic mechanism of visual system plasticity. Because myelination plays an important role in axonal conduction velocities, spike-time arrival, and neural synchrony, activity-dependent myelination may play a dynamic role in ocular dominance plasticity, contributing to synaptic plasticity driven by visual experience, as first described in the pioneering studies of Hubel and Wiesel.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.