In vitro and in vivo studies of perineuronal glycosaminoglycans in synaptic functions

Abstract

Perineuronal nets (PN) as detected by lectin (Wisteria floribunda agglutinin) binding are enriched in chondroitin sulfate and heparan sulfate moieties. We hypothesize that these perineuronal glycosaminoglycan moieties play roles in the regulation of synaptic functions. We first tested for induction of long-term potentiation (LTP) as an indicator of plasticity of synaptic efficacy in the Schaffer collateral pathway of hippocampal slice preparations of P20 rats. Treatment with chondroitinase or heparitinases resulted in dose-dependent decline in LTP induction, thus suggesting importance of perineuronal glycosaminoglycans for facilitation of synaptic plasticity. We next tested for physiological modulations of the PN in plastic stages of vestibular development or vestibular compensation following labyrinthectomy. In the vestibular nuclei (VN) of rats, we found that the diffuse organization of PN in neonates consolidated into network structures enclosing GABAergic neurons (PN-neurons) by P21. Following bilateral labyrinthectomy in neonatal rats, we found significant decline in PN-neurons, persisting into adulthood. This indicates that PN formation in the VN is dependent on sensory inputs. Unilateral labyrinthectomy performed in the adult however resulted in return of PN to fuzziness coincident with vestibular compensation before the resumption of PN consolidation. Structural reorganization of the PN is therefore coordinated with compensatory adjustments in the vestibular circuit. With further work on glycosaminoglycan moieties that are involved in the PN reorganization, our work will reveal the functional importance of perineuronal glycosaminoglycans to the plasticity of neural circuits.