Development of parvalbumin neurons and perineuronal nets in the visual cortex of normal and dark-exposed cats.

During development, the visual system maintains a high capacity for modification by expressing characteristics permissive for plasticity, enabling neural circuits to be refined by visual experience to achieve their mature form. This period is followed by the emergence of characteristics that stabilize the brain to consolidate for lifetime connections that were informed by experience. Attenuation of plasticity potential is thought to derive from an accumulation of plasticity-inhibiting characteristics that appear at ages beyond the peak of plasticity. Perineuronal nets (PNNs) are molecular aggregations that primarily surround fast-spiking inhibitory neurons called parvalbumin (PV) cells, which exhibit properties congruent with a plasticity inhibitor. In this study, we examined the development of PNNs and PV cells in the primary visual cortex of a highly visual mammal, and assessed the impact that 10 days of darkness had on both characteristics. Here, we show that labeling for PV expression emerges earlier and reaches adult levels sooner than PNNs. We also demonstrate that darkness, a condition known to enhance plasticity, significantly reduces the density of PNNs and the size of PV cell somata but does not alter the number of PV cells in the visual cortex. The darkness-induced reduction of PV cell size occurred irrespective of whether neurons were surrounded by a PNN, suggesting that PNNs have a restricted capacity to inhibit plasticity. Finally, we show that PV cells surrounded by a PNN were significantly larger than those without one, supporting the view that PNNs may mediate trophic support to the cells they surround.

Retinal and Optic Nerve Integrity Following Monocular Inactivation for the Treatment of Amblyopia.

In animal models, monocular deprivation (MD) by lid closure mimics the effects of unilateral amblyopia in humans. Temporary inactivation of one or both eyes with intraocular administration of tetrodotoxin (TTX) has recently been shown to promote recovery from the anatomical effects of MD at post-critical period ages when standard recovery strategies fail. In the current study, the retinae and optic nerves of animals subjected to 10 days of monocular retinal inactivation were assessed for pathological changes as a means of assessing the viability of this potential new amblyopia therapy. Retinal sections from both eyes were subjected to hematoxylin and eosin staining and were then examined for cell density and soma size in the ganglion cell layer (GCL). Sections of the optic nerve from each eye were examined for neurofilament protein, myelin, glial cell density, and glial fibrillary acidic protein (GFAP). Our study revealed no evidence of gross histopathological abnormalities following inactivation for 10 days, nor was there evidence of degeneration of axons or loss of myelin in the optic nerve serving inactivated eyes. On all measurements, the inactivated eye was indistinguishable from the fellow eye, and both were comparable to normal controls. We confirmed that our inactivation protocol obliterated visually-evoked potentials for 10 consecutive days, but visual responses were restored to normal after the effects of inactivation wore off. Notwithstanding the critical need for further assessment of ocular and retinal health following inactivation, these results provide evidence that retinal inactivation as a treatment for amblyopia does not produce significant retinal damage or degeneration.