Enzymatic degradation of cortical perineuronal nets reverses GABAergic interneuron maturation

Willis, A., Pratt, J. A. and Morris, B. J. (2022) Enzymatic degradation of cortical perineuronal nets reverses GABAergic interneuron maturation. Molecular Neurobiology, 59(5), pp. 2874-2893. (doi: 10.1007/s12035-022-02772-z) (PMID:35233718)

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Perineuronal nets (PNNs) are specialised extracellular matrix structures which preferentially enwrap fast-spiking (FS) parvalbumin interneurons and have diverse roles in the cortex. PNN maturation coincides with closure of the critical period of cortical plasticity. We have previously demonstrated that BDNF accelerates interneuron development in a c-Jun-NH2-terminal kinase (JNK)–dependent manner, which may involve upstream thousand-and-one amino acid kinase 2 (TAOK2). Chondroitinase-ABC (ChABC) enzymatic digestion of PNNs reportedly reactivates ‘juvenile-like’ plasticity in the adult CNS. However, the mechanisms involved are unclear. We show that ChABC produces an immature molecular phenotype in cultured cortical neurons, corresponding to the phenotype prior to critical period closure. ChABC produced different patterns of PNN-related, GABAergic and immediate early (IE) gene expression than well-characterised modulators of mature plasticity and network activity (GABAA-R antagonist, bicuculline, and sodium-channel blocker, tetrodotoxin (TTX)). ChABC downregulated JNK activity, while this was upregulated by bicuculline. Bicuculline, but not ChABC, upregulated Bdnf expression and ERK activity. Furthermore, we found that BDNF upregulation of semaphorin-3A and IE genes was TAOK mediated. Our data suggest that ChABC heightens structural flexibility and network disinhibition, potentially contributing to ‘juvenile-like’ plasticity. The molecular phenotype appears to be distinct from heightened mature synaptic plasticity and could relate to JNK signalling. Finally, we highlight that BDNF regulation of plasticity and PNNs involves TAOK signalling.

Item Type:Articles
Additional Information:The authors would like to thank the University of Glasgow, College of Medical Veterinary and Life Sciences Doctoral Training Programme for funding this work.
Glasgow Author(s) Enlighten ID:Pratt, Dr Judith and Willis, Ashleigh and Morris, Professor Brian
Authors: Willis, A., Pratt, J. A., and Morris, B. J.
College/School:College of Medical Veterinary and Life Sciences > School of Psychology & Neuroscience
Journal Name:Molecular Neurobiology
ISSN (Online):1559-1182
Published Online:01 March 2022
Copyright Holders:Copyright © 2022 The Authors
First Published:First published in Molecular Neurobiology 59(5): 2874-2893
Publisher Policy:Reproduced under a Creative Commons License

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