Regulatory roles of perineuronal nets and semaphorin 3A in the postnatal maturation of the central vestibular circuitry for graviceptive reflex
Perineuronal nets (PN) restrict neuronal plasticity in the adult brain. We hypothesize that activity-dependent consolidation of PN is required for functional maturation of behavioral circuits. Using the postnatal maturation of brainstem vestibular nucleus (VN) circuits as a model system, we report a neonatal period in which consolidation of central vestibular circuitry for graviception is accompanied by activity-dependent consolidation of chondroitin sulfate (CS)-rich PN around GABAergic neurons in the VN. Postnatal onset of negative geotaxis was used as an indicator for functional maturation of vestibular circuits. Rats display negative geotaxis from postnatal day (P) 9, coinciding with the condensation of CS-rich PN around GABAergic interneurons in the VN. Delaying PN formation, by removal of primordial CS moieties on VN with chondroitinase ABC (ChABC) treatment at P6, postponed emergence of negative geotaxis to P13. Similar postponement was observed following inhibition of GABAergic transmission with bicuculline, in line with the reported role of PN in increasing excitability of parvalbumin neurons. We further reasoned that PN-CS restricts bioavailability of plasticity-inducing factors such as semaphorin 3A (Sema3A) to bring about circuit maturation. Treatment of VN explants with ChABC to liberate PN-bound Sema3A resulted in dendritic growth and arborization, implicating structural plasticity that delays synapse formation. Evidence is thus provided for the role of PN-CS–Sema3A in regulating structural and circuit plasticity at VN interneurons with impacts on the development of graviceptive postural control.
KeywordsPerineuronal chondroitin sulfates Semaphorin 3A Vestibular system Development
The authors are grateful to Simon S.M. Chan, Kimmy F.L. Tsang and Alice Y.Y. Lui of The University of Hong Kong for their excellent assistance in the experiments.
This work was supported by grants of the Hong Kong Research Grants Council (RGC HKU77681212, 17125115, N_HKU735/14).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures performed in studies involving animals were in accordance with the ethical standard of the institution of practice at which the studies were conducted. All animal protocols and procedures were performed in accordance to the Guide for the Care and Use of Laboratory Animals (NIH, 2011) and approved by The University of Hong Kong Committee on the Use of Live Animals in Teaching and Research. This article does not contain any human participants performed by any of the authors.
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