title: Maturation of cortical circuits requires Semaphorin 7A.
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.
authors.affiliation: 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.
authors.forename: Ioana
authors.initials: I
authors.lastname: Carcea
authors.affiliation: Departments of Neuroscience and Friedman Brain Institute.
authors.forename: Shekhar B
authors.initials: SB
authors.lastname: Patil
authors.affiliation: Departments of Neuroscience and Friedman Brain Institute, Department of Physiology, Michigan State University, East Lansing, MI 48824.
authors.forename: Alfred J
authors.initials: AJ
authors.lastname: Robison
authors.affiliation: Departments of Neuroscience and Friedman Brain Institute.
authors.forename: Roxana
authors.initials: R
authors.lastname: Mesias
authors.affiliation: Departments of Pharmaceutical Sciences and Pediatrics, University of Colorado, Anschutz Medical Campus, Aurora, CO 80045;
authors.forename: Molly M
authors.initials: MM
authors.lastname: Huntsman
authors.affiliation: 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.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Froemke
authors.affiliation: Friedman Brain Institute, Seaver Autism Center, and Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029; Psychiatry.
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Buxbaum
authors.affiliation: 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.
authors.forename: George W
authors.initials: GW
authors.lastname: Huntley
authors.affiliation: 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.
authors.forename: Deanna L
authors.initials: DL
authors.lastname: Benson
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D005071:Evoked Potentials / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009415:Nerve Net / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D039961:Semaphorins / Q000235:genetics / Q000378:metabolism*; D013003:Somatosensory Cortex / Q000166:cytology / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D015703:Antigens, CD; C485571:Sema7a protein, mouse; C558466:Sema7a protein, rat; D039961:Semaphorins
keywords: E/I balance; EPSPs; IPSPs; critical period; thalamocortical