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Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions

Author

Listed:
  • Karen Perez Arce

    (Tufts University School of Medicine
    Novartis Institutes for Biomedical Research)

  • Adema Ribic

    (Tufts University School of Medicine
    University of Virginia)

  • Dhrubajyoti Chowdhury

    (Yale School of Medicine)

  • Katherine Watters

    (Tufts University School of Medicine
    Yale School of Medicine)

  • Garth J. Thompson

    (Yale School of Medicine
    ShanghaiTech University)

  • Basavaraju G. Sanganahalli

    (Yale School of Medicine)

  • Elizabeth T. C. Lippard

    (Yale School of Medicine
    University of Texas)

  • Astrid Rohlmann

    (Westfälische Wilhelms-University)

  • Stephen M. Strittmatter

    (Yale School of Medicine
    Yale School of Medicine)

  • Markus Missler

    (Westfälische Wilhelms-University)

  • Fahmeed Hyder

    (Yale School of Medicine)

  • Thomas Biederer

    (Tufts University School of Medicine
    Yale School of Medicine)

Abstract

Multiple trans-synaptic complexes organize synapse development, yet their roles in the mature brain and cooperation remain unclear. We analyzed the postsynaptic adhesion protein LRRTM1 in the prefrontal cortex (PFC), a region relevant to cognition and disorders. LRRTM1 knockout (KO) mice had fewer synapses, and we asked whether other synapse organizers counteract further loss. This determined that the immunoglobulin family member SynCAM 1 controls synapse number in PFC and was upregulated upon LRRTM1 loss. Combined LRRTM1 and SynCAM 1 deletion substantially lowered dendritic spine number in PFC, but not hippocampus, more than the sum of single KO impairments. Their cooperation extended presynaptically, and puncta of Neurexins, LRRTM1 partners, were less abundant in double KO (DKO) PFC. Electrophysiology and fMRI demonstrated aberrant neuronal activity in DKO mice. Further, DKO mice were impaired in social interactions and cognitive tasks. Our results reveal concerted roles of LRRTM1 and SynCAM 1 across synaptic, network, and behavioral domains.

Suggested Citation

  • Karen Perez Arce & Adema Ribic & Dhrubajyoti Chowdhury & Katherine Watters & Garth J. Thompson & Basavaraju G. Sanganahalli & Elizabeth T. C. Lippard & Astrid Rohlmann & Stephen M. Strittmatter & Mark, 2023. "Concerted roles of LRRTM1 and SynCAM 1 in organizing prefrontal cortex synapses and cognitive functions," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36042-w
    DOI: 10.1038/s41467-023-36042-w
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