Perineuronal chondroitin sulfates reinforce inhibitory GABAergic transmission in the maturation of sensori-motor function

Abstract

Introduction: The last steps in the maturation of sensori-motor functions are often subject to experiencedependent modulations. In rats, we observed onset of negative geotaxis (an innate behavior indicative of graviception) as from postnatal day (P)9, time-matched with the consolidation of chondroitin sulfate (CS)-rich perineuronal nets (PN) around GABAergic/parvalbuminexpressing neurons in the vestibular nucleus (VN). Experience-dependent plasticity was revealed when bilateral labyrinthectomy in neonates significantly deterred both the onset of negative geotaxis and the consolidation of PN-CS around GABAergic interneurons in the VN. Materials and Methods: Using SD rats as model, negative geotaxis and air righting were investigated as behavioural readout of graviception. Whole-cell patch-clamp recordings were performed on VN interneurons in brainstem slice at P9 and P14 to investigate spontaneous inhibitory and excitatory post-synaptic GABA or AMPA receptor-mediated current (sIPSC and sEPSC) and EPSC/IPSC ratio. Results and Discussion: In labyrinth-intact rats, treatment of the VN at P6 with chondroitinase ABC (ChABC) resulted in loss of PN-CS. The effect lasted up to P13 during which developmental onset of negative geotaxis was delayed to P13. Is PN-CS critical for hardwiring inhibitory GABAergic transmission in the postnatal vestibular circuit? With whole-cell patch-clamp recordings performed on VN interneurons in brainstem slice preparations at P9 and P14 when PN-CS underwent consolidation, we found significant increase in frequency of sIPSC. Pretreatment of the VN with ChABC at P6 led to 50% reduction in frequencies of IPSCs both at P9 and P14 but no accompanying change in amplitude of sIPSC. After acute ChABC treatment, significant increase of EPSC/IPSC ratio for frequency but not for amplitude per sampled neuron was likewise observed. In contrast, neither frequency nor amplitude of sEPSC showed significant change in this period. Support is thus provided for a role of PNCS in reinforcing inhibitory/GABAergic inputs to VN interneurons in the maturation of the vestibular pathway for the graviceptive behaviour.