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Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity

Nature Neuroscience volume 10, pages 1569–1577 (2007)Cite this article

Abstract

Functional maturation of GABAergic innervation in the developing visual cortex is regulated by neural activity and sensory inputs and in turn influences the critical period of ocular dominance plasticity. Here we show that polysialic acid (PSA), presented by the neural cell adhesion molecule, has a role in the maturation of GABAergic innervation and ocular dominance plasticity. Concentrations of PSA significantly decline shortly after eye opening in the adolescent mouse visual cortex; this decline is hindered by visual deprivation. The developmental and activity-dependent regulation of PSA expression is inversely correlated with the maturation of GABAergic innervation. Premature removal of PSA in visual cortex results in precocious maturation of perisomatic innervation by basket interneurons, enhanced inhibitory synaptic transmission, and earlier onset of ocular dominance plasticity. The developmental and activity-dependent decline of PSA expression therefore regulates the timing of the maturation of GABAergic inhibition and the onset of ocular dominance plasticity.

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Figure 1: PSA expression declines shortly after eye opening in mouse visual cortex.
Figure 2: Visual experience downregulates PSA expression in mouse visual cortex.
Figure 3: Premature reduction of PSA expression promotes maturation of perisomatic GABAergic synapses in cortical organotypic cultures.
Figure 4: Premature reduction of PSA expression promotes localization of GAD65 to presynaptic boutons of basket cells.
Figure 5: Premature reduction of PSA expression in visual cortex promotes functional maturation of GABAergic but not glutamatergic synapses.
Figure 6: Premature reduction of PSA expression in visual cortex induces precocious onset of the critical period for ocular dominance plasticity.

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Acknowledgements

We thank P. Wu, E. Putignano, N. Berardi and J. Boehm for technical assistance and discussion; and E. Ruthazer for critically reading the manuscript. This work was supported by the National Institutes of Health (RO1 EY 13564-01). G.D.C. has a National Association for Research in Schizophrenia and Depression (NARSAD) Young Investigator Award founded by the Forrest C. Lattner Foundation. Z.J.H. is a Pew and McKnight Scholar.

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Author notes

  1. Graziella Di Cristo & Bidisha Chattopadhyaya

    Present address: Present addresses: CHU Sainte-Justine – Université de Montréal, Montreal, Quebec, Canada (G.D.C.); Friedrich Miescher Institute, Novartis Research Foundation, Basel, Switzerland (B.C.).,

Authors and Affiliations

  1. Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York, 11734, USA

    Graziella Di Cristo, Bidisha Chattopadhyaya, Sandra J Kuhlman, Yu Fu, Cai Zhi Wu & Z Josh Huang

  2. Neuroscience Program, State University of New York, Stony Brook, 11790, New York, USA

    Bidisha Chattopadhyaya

  3. Centre Hospitalier Universitaire (CHU) Sainte-Justine – Université de Montréal, 3715 CÂte-Ste-Catherine, Montreal, H3T IC5, Canada

    Marie-Claude Bélanger

  4. Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, 10021, USA

    Urs Rutishauser

  5. Instituto di Neurofisiologia del Centro Nazionale della Ricerca, via G. Moruzzi 1, 56124, Pisa, Italy

    Lamberto Maffei

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Contributions

G.D.C. and Z.J.H. conceived and organized the project and wrote the manuscript. G.D.C. conducted most of the experiments. B.C. contributed to the in vitro and in vivo morphological studies. S.J.K. and Y.F. carried out the mPSC recordings. M.-C.B. performed the western blotting. C.Z.W. contributed to the PSA expression analysis in vivo. U.R. provided endoN and advice. L.M. provided the facility for dark rearing and VEP recording.

Corresponding author

Correspondence to Z Josh Huang.

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Di Cristo, G., Chattopadhyaya, B., Kuhlman, S. et al. Activity-dependent PSA expression regulates inhibitory maturation and onset of critical period plasticity. Nat Neurosci 10, 1569–1577 (2007). https://doi.org/10.1038/nn2008

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