Dynamics of perineuronal net-associated plastic factors after sensory loss

Abstract

The vestibular nucleus offers a unique window into re-opening circuit plasticity for equilibrium reflexes. Following unilateral labyrinthectomy (UL) to perturb sensory inputs to the central vestibular nucleus in adult rats, we observed correction of equilibrium reflexes within 2 weeks, suggesting spontaneous reorganization of otherwise stable vestibular circuits to compensate for the imbalance of bilateral inputs. Perineuronal nets (PNN) that form around vestibular interneurons in mature circuits were decompacted within 5 days post- UL but were reconsolidated with vestibular compensation. We then hypothesized that the perineuronal chondroitin sulphate proteoglycans (CSPGs) entrap plasticity-inducing factors that can be tapped to re-open plasticity in mature circuits. Analysis of hindbrain CSPG composition over the course of vestibular compensation found increase in 2, 4-disulphated disaccharides and decrease in 4-sulphated disaccharides during day 1 – 14 post-UL. In addition, there was marked increase in non-sulphated disaccharides during day 3 – 7 post-UL followed by return to basal levels. Do changes in sulphation pattern of the CS moieties impact on the repertoire of PNN-associated plasticity-inducing or -limiting factors? To this end, we developed a novel protocol for specific labeling and targeted recovery of PNNCSPGs in the vestibular nucleus. Fluorescent staining and Western blot analysis demonstrated the specificity of our protocol in labeling and recovery PNNassociated aggrecan, thus allowing the pursuit of PNN-CS sulphation pattern and PNN-associated proteome analysis . Results will advance knowledge of molecular and cellular mechanisms that modulate neural circuit plasticity, and inform strategies for correcting developmentally mis-wired circuits or for rehabilitation in age-related cognitive disabilities. (Supported: GRF17125115, 17131816)