The regulatory roles of semaphorin 3A and chondroitin sulfates on perineuronal nets in the developing vestibular circuitry

Abstract

Perineuronal nets (PN) were crucial for restricting neuronal plasticity during development. Our study of the central vestibular nucleus (VN) found consolidation of PN around GABAergic interneurons as from postnatal day (P)9 of Sprague Dawley (SD) rats. This was accompanied by progressive localization of semaphorin 3A (Sema3A) to chondroitin sulphate moieties (CS) of PN. We hypothesized that PN-CS binding of Sema3A limits the action of Sema3A as a plasticity-inducing factor in the VN. We tested for structural plasticity in VN explant cultures, treated with Chondroitinase ABC (ChABC) and/ or Sema3A. Parallel cultures were fixed for assessment of neurite arborization and growth. Increase in these parameters suggested involvement of CS and Sema3A in the structural plasticity of VN neurons. To study the impact of PN-CS/Sema3A at the circuit level, the SD rats were assessed for the emergence of negative geotaxis as a readout for graviception. We observed negative geotaxis as early as P9, in correlation with consolidation of PN around GABAergic neurons in the VN. ChABC/Sema3A-treated rats showed delayed emergence of negative geotaxis, similar to effects of bicuculline but contrasting those of muscimol. Delayed emergence of negative geotaxis also correlated to the postponed formation of PN after ChABC treatment. Our results suggest that trapping of plasticity-inducing Sema3A onto PN-CS translates to the closure of plasticity in the graviceptive circuit. [Grant Support: HKRGC17125115M & 777911M]