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Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations

Author

Listed:
  • Julie Jézéquel

    (King’s College London
    King’s College London)

  • Giuseppe Condomitti

    (King’s College London
    King’s College London)

  • Tim Kroon

    (King’s College London
    King’s College London)

  • Fursham Hamid

    (King’s College London
    King’s College London)

  • Stella Sanalidou

    (King’s College London
    King’s College London)

  • Teresa Garcés

    (King’s College London
    King’s College London)

  • Patricia Maeso

    (King’s College London
    King’s College London)

  • Maddalena Balia

    (King’s College London
    King’s College London)

  • Zhaohui Hu

    (King’s College London
    King’s College London)

  • Setsuko Sahara

    (King’s College London
    King’s College London)

  • Beatriz Rico

    (King’s College London
    King’s College London)

Abstract

GABAergic interneurons were thought to regulate excitatory networks by establishing unselective connections onto diverse pyramidal cell populations, but recent studies demonstrate the existence of a cell type-specific inhibitory connectome. How and when interneurons establish precise connectivity patterns among intermingled populations of excitatory neurons remains enigmatic. We explore the molecular mechanisms orchestrating the emergence of cell type-specific inhibition in the mouse cerebral cortex. We demonstrate that layer 5 intra- (L5 IT) and extra-telencephalic (L5 ET) neurons express unique transcriptional programs, allowing them to shape parvalbumin- (PV+) and cholecystokinin-positive (CCK+) interneuron wiring. We identified Cdh12 and Cdh13, two cadherin superfamily members, as underpinnings of cell type- and input-specific inhibitory patterns of L5 pyramidal cell populations. Multiplex monosynaptic tracing revealed a minimal overlap between IT and ET presynaptic inhibitory networks and suggests that different PV+ basket cell populations innervate distinct L5 pyramidal cell types. Here, we unravel the contribution of cadherins in shaping cell-type-specific cortical interneuron wiring.

Suggested Citation

  • Julie Jézéquel & Giuseppe Condomitti & Tim Kroon & Fursham Hamid & Stella Sanalidou & Teresa Garcés & Patricia Maeso & Maddalena Balia & Zhaohui Hu & Setsuko Sahara & Beatriz Rico, 2025. "Cadherins orchestrate specific patterns of perisomatic inhibition onto distinct pyramidal cell populations," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59635-z
    DOI: 10.1038/s41467-025-59635-z
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    References listed on IDEAS

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    1. Brenda L. Bloodgood & Nikhil Sharma & Heidi Adlman Browne & Alissa Z. Trepman & Michael E. Greenberg, 2013. "The activity-dependent transcription factor NPAS4 regulates domain-specific inhibition," Nature, Nature, vol. 503(7474), pages 121-125, November.
    2. Ee-Lynn Yap & Noah L. Pettit & Christopher P. Davis & M. Aurel Nagy & David A. Harmin & Emily Golden & Onur Dagliyan & Cindy Lin & Stephanie Rudolph & Nikhil Sharma & Eric C. Griffith & Christopher D., 2021. "Bidirectional perisomatic inhibitory plasticity of a Fos neuronal network," Nature, Nature, vol. 590(7844), pages 115-121, February.
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