Regulatory role of perineuronal nets and semaphorin 3A in the developmental maturation of the central vestibular circuitry

Abstract

During the formative period of neural circuits, perineuronal nets (PN) are established to restrict plasticity of the circuit. The emergence of negative geotaxis with postnatal maturation of the vestibular circuitry for gravity detection offers a behavioral readout in tests for roles of PN in vestibular plasticity.

Using rats as model, we observed that negative geotaxis was mature by postnatal day (P) 9, in correlation with consolidation of PN around GABAergic neurons in the vestibular nucleus (VN). Treatment of the VN at P6 with chondroitinase ABC (ChABC) cleaved chondroitin sulfate (CS) moieties of PN and delayed emergence of negative geotaxis to P13. Delay to P13 was also observed following the treatment of the VN with a GABAA receptor antagonist, reinforcing GABAergic transmission as regulated by perineuronal CS is a crucial step for the maturation of negative geotaxis.

Throughout postnatal development of the VN, CS moieties of PN colocalized with semaphoring 3A (Sema3A), a secreted glycoprotein that regulates neuronal polarization. The expression of Sema3A in VN neurons was confirmed by in-situ hybridization and immunocytochemistry. In addition, Sema3A regulated the dendrite growth pattern of GABAergic neurons in VN. We infer the morphological changes of the dendritic arbor can contribute to the vestibular plasticity.

Our results suggest that, as the VN circuitry undergoes maturation, perineuronal CS moieties retain Sema3A and limit the participation of Sema3A in the modulation of morphological and functional properties of GABAergic interneurons in the VN, thereby contributing to the hardwiring of the central pathway for vestibular behavior. [Grant Supported by HKRGC 774608M & 777911M]