Roles of perineuronal matrix in developmental plasticity of the central vestibular system

Abstract

Perineuronal nets (PN), as detectable by Wisteria floribunda agglutinin (WFA) staining, are extracellular matrix molecules surrounding GABAergic neurons. We hypothesize that PN regulate developmental plasticity of central vestibular circuitry containing GABAergic neurons. To address this, we looked for changes in PN during postnatal development of the central vestibular system. WFA-stained PN in the vestibular nucleus (VN) changed from diffuse organization in neonates to consolidated network in adults. Previous studies suggested that PN formation is activity-dependent. Therefore, the effect of vestibular deprivation on PN development in the VN was also investigated. Following bilateral labyrinthectomy (BL) at P3, the number of VN neurons with PN at adult stage was less than in normal controls. However, following BL at P7 or later, the number of PN-bound VN neurons were similar to normal controls. Our findings indicate that the first postnatal week is a critical period during which inputs from the peripheral afferents provide the necessary trigger for PN formation. The relationship between PN formation and maturation of vestibular functions was further studied with a behavioral test for negative geotaxis (a vestibular reflex). Normal rats acquired the mature response at P9, the time when PN consolidation was first observed. However, the acquisition was delayed to P13 in rats pretreated with chondroitinase ABC injection into the VN at P6 to prevent PN formation. Therefore, PN consolidation in the VN is critical to timely acquisition of the vestibular reflex. Taken together, our results show that PN undergo activity-dependent reorganization that corresponds to the maturation of vestibular behavior, indicating that PN play important roles in plasticity of the developing central vestibular system.