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Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice

Author

Listed:
  • Elise C. Cope

    (Princeton University
    University of Virginia School of Medicine)

  • Samantha H. Wang

    (Princeton University)

  • Renée C. Waters

    (Princeton University)

  • Isha R. Gore

    (Princeton University)

  • Betsy Vasquez

    (Princeton University)

  • Blake J. Laham

    (Princeton University)

  • Elizabeth Gould

    (Princeton University)

Abstract

Mutation or deletion of the SHANK3 gene, which encodes a synaptic scaffolding protein, is linked to autism spectrum disorder and Phelan-McDermid syndrome, conditions associated with social memory impairments. Shank3B knockout mice also exhibit social memory deficits. The CA2 region of the hippocampus integrates numerous inputs and sends a major output to the ventral CA1 (vCA1). Despite finding few differences in excitatory afferents to the CA2 in Shank3B knockout mice, we found that activation of CA2 neurons as well as the CA2-vCA1 pathway restored social recognition function to wildtype levels. vCA1 neuronal oscillations have been linked to social memory, but we observed no differences in these measures between wildtype and Shank3B knockout mice. However, activation of the CA2 enhanced vCA1 theta power in Shank3B knockout mice, concurrent with behavioral improvements. These findings suggest that stimulating adult circuitry in a mouse model with neurodevelopmental impairments can invoke latent social memory function.

Suggested Citation

  • Elise C. Cope & Samantha H. Wang & Renée C. Waters & Isha R. Gore & Betsy Vasquez & Blake J. Laham & Elizabeth Gould, 2023. "Activation of the CA2-ventral CA1 pathway reverses social discrimination dysfunction in Shank3B knockout mice," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37248-8
    DOI: 10.1038/s41467-023-37248-8
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