NMDA receptors control development of somatosensory callosal axonal projections

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Abstract

Callosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is GluN2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and works with the EPHRIN-B/EPHB system. Thus, NMDAR in target S1 cortex regulates the formation callosal circuits perhaps by modulating EPH-dependent repulsion.

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All data generated or analyses during this study are included in the manuscript.

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Jing Zhou

Department of Neurology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Yong Lin

Department of Neurology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Trung Huynh

Department of Neurology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.
Hirofumi Noguchi

Department of Neurology, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-9779-4956
Jeffrey Ohmann Bush

Cell and Tissue Biology and Program in Craniofacial Biology, Institute for human genetics, University of California, San Francisco, San Francisco, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-6053-8756
Samuel Pleasure

Neuroscience, University of California, San Francisco, San Francisco, United States

For correspondence
samuel.pleasure@ucsf.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0001-8599-1613

Funding

National Institute of Mental Health (R01MH119435)

Jing Zhou
Yong Lin
Trung Huynh
Hirofumi Noguchi
Samuel Pleasure

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AN176415) of the University of California San Francisco.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.