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Proc Natl Acad Sci U S A. 2014 Sep 23;111(38):13978-83. doi: 10.1073/pnas.1408680111. Epub 2014 Sep 8.

Maturation of cortical circuits requires Semaphorin 7A.

Author information

1
Departments of Neuroscience and Friedman Brain Institute, Seaver Autism Center, and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Departments of Otolaryngology, Physiology and Neuroscience, Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016; and.
2
Departments of Neuroscience and Friedman Brain Institute.
3
Departments of Neuroscience and Friedman Brain Institute, Department of Physiology, Michigan State University, East Lansing, MI 48824.
4
Departments of Pharmaceutical Sciences and Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045;
5
Departments of Otolaryngology, Physiology and Neuroscience, Molecular Neurobiology Program, The Helen and Martin Kimmel Center for Biology and Medicine at the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016; and.
6
Friedman Brain Institute, Seaver Autism Center, and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Psychiatry.
7
Departments of Neuroscience and Friedman Brain Institute, Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; george.huntley@mssm.edu deanna.benson@mssm.edu.

Abstract

Abnormal cortical circuits underlie some cognitive and psychiatric disorders, yet the molecular signals that generate normal cortical networks remain poorly understood. Semaphorin 7A (Sema7A) is an atypical member of the semaphorin family that is GPI-linked, expressed principally postnatally, and enriched in sensory cortex. Significantly, SEMA7A is deleted in individuals with 15q24 microdeletion syndrome, characterized by developmental delay, autism, and sensory perceptual deficits. We studied the role that Sema7A plays in establishing functional cortical circuitry in mouse somatosensory barrel cortex. We found that Sema7A is expressed in spiny stellate cells and GABAergic interneurons and that its absence disrupts barrel cytoarchitecture, reduces asymmetrical orientation of spiny stellate cell dendrites, and functionally impairs thalamocortically evoked synaptic responses, with reduced feed-forward GABAergic inhibition. These data identify Sema7A as a regulator of thalamocortical and local circuit development in layer 4 and provide a molecular handle that can be used to explore the coordinated generation of excitatory and inhibitory cortical circuits.

KEYWORDS:

E/I balance; EPSPs; IPSPs; critical period; thalamocortical

PMID:
25201975
PMCID:
PMC4183324
DOI:
10.1073/pnas.1408680111
[Indexed for MEDLINE]
Free PMC Article

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