Chondroitin Sulfate Is Required for Onset and Offset of Critical Period Plasticity in Visual Cortex

Xubin Hou,Kenji Sakimura,Nozomu Yoshioka,Takao K Hensch,Hiroshi Kitagawa,Hiroaki Tsukano,Katsuei Shibuki,Yuchio Yanagawa,Sayaka Sugiyama,Akiko Sakai,Kosei Takeuchi,Shinji Miyata,Michihiro Igarashi,Yumi Watanabe

doi:10.1038/s41598-017-04007-x

Abstract

Ocular dominance plasticity is easily observed during the critical period in early postnatal life. Chondroitin sulfate (CS) is the most abundant component in extracellular structures called perineuronal nets (PNNs), which surround parvalbumin-expressing interneurons (PV-cells). CS accumulates in PNNs at the critical period, but its function in earlier life is unclear. Here, we show that initiation of ocular dominance plasticity was impaired with reduced CS, using mice lacking a key CS-synthesizing enzyme, CSGalNAcT1. Two-photon in vivo imaging showed a weaker visual response of PV-cells with reduced CS compared to wild-type mice. Plasticity onset was restored by a homeoprotein Otx2, which binds the major CS-proteoglycan aggrecan and promotes its further expression. Continuous CS accumulation together with Otx2 contributed bidirectionally to both onset and offset of plasticity, and was substituted by diazepam, which enhances GABA function. Therefore, CS and Otx2 may act as common inducers of both onset and offset of the critical period by promoting PV-cell function throughout the lifetime.

Highlights

The onset of the critical period occurs with maturation of cortical GABA circuits[4,5]
To confirm whether T1 is responsible for chondroitin sulfate (CS) synthesis in V1, we biochemically characterized CS that is post-translationally attached to a core protein of proteoglycans[27]
During perineuronal nets (PNNs) formation in V1, impaired CS biosynthesis resulted in a weakened fluorescence intensity of Wisteria floribunda agglutinin (WFA)-labeled GAGs by more than half (Fig. 1D, E, I) and a reduced number of labeled cells in supragranular layers of the binocular zone (Fig. 1H: WT versus KO, 3–4 mice, p < 0.01 for P16–18; p < 0.0001 for P28–30; p < 0.05 for >P60, ANOVA)

Summary

Introduction

The onset of the critical period occurs with maturation of cortical GABA circuits[4,5]. Among multiple subsets of GABAergic interneurons, accumulating evidence indicates the involvement of fast-spiking, parvalbumin-expressing basket cells (PV-cells) These cells provide somatic inhibition to regulate the response gain of their target neurons[6] and respond according to an imbalance in visual experience, triggering plasticity[7,8,9]. Adult plasticity following prolonged MD facilitates potentiation of open eye responses without amblyopic depression of responses to the closed eye[18] Inhibitory circuits such as vasoactive intestinal peptide (VIP)- or somatostatin (SST)-positive interneurons are required for adult plasticity, whereas the requirement for PV-cells is controversial[19,20]. The possibility that the same molecules act to modulate both onset and offset of plasticity cannot be ruled out

Methods

Results

Conclusion