Article

Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus

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Abstract

During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses within V1, specifically those containing the GABAA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.

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Acknowledgements

We thank C. Lohmann and C. Niell for the critical reading of the manuscript, E. Ruimschotel for technical assistance, and Y. Nakagawa and A. McGee for providing the Olig3-cre mouse line. This project has received funding from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement No. 720270 (HBP SGA1). It was further funded through a grant from AgentschapNL to the NeuroBasic PharmaPhenomics consortium (C.N.L.), a NWO grant (823.02.001) to C.N.L., a grant from Stichting Blindenhulp, a donation from Praktijkgenerator b.v., a Veni grant from the NWO to R.M. (863.12.006) and a Vidi grant from the NWO to J.A.H. (864.10.010).

Author information

Author notes

  1. Jean-Pierre Sommeijer and Mehran Ahmadlou contributed equally to this work.

Affiliations

  1. Department of Molecular Visual Plasticity, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

    • Jean-Pierre Sommeijer
    • , M. Hadi Saiepour
    • , Koen Seignette
    • , Rogier Min
    •  & Christiaan N. Levelt
  2. Department of Cortical Structure and Function, Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands

    • Mehran Ahmadlou
    •  & J. Alexander Heimel
  3. Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, VU University Amsterdam, Amsterdam, The Netherlands

    • Christiaan N. Levelt

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Contributions

J.-P.S. and K.S. performed immunohistochemical analyses; J.-P.S. and M.H.S. performed intrinsic signal imaging; J.-P.S. did western blot analyses; M.A. performed the in vivo electrophysiology; R.M. performed slice electrophysiology; J.P.S., M.A., M.H.S., K.S. and R.M. conceived the experiments, performed data analyses and helped writing the manuscript; J.A.H. developed analysis tools, performed data analyses and helped with the writing; C.N.L. conceived the research line, oversaw the project and wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Christiaan N. Levelt.

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