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Inhibition mediated by group III metabotropic glutamate receptors regulates habenula activity and defensive behaviors

Author

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  • Anna Maria Ostenrath

    (Norwegian University of Science and Technology)

  • Nicholas Faturos

    (Norwegian University of Science and Technology
    University of Minnesota School of Medicine)

  • Yağnur Işık Çiftci Çobanoğlu

    (Norwegian University of Science and Technology
    Koç University School of Medicine)

  • Bram Serneels

    (Norwegian University of Science and Technology)

  • Inyoung Jeong

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Ekin Dongel Dayanc

    (Norwegian University of Science and Technology
    Acibadem Mehmet Ali Aydinlar University)

  • Anja Enz

    (Department of Molecular Life Sciences)

  • Francisca Hinrichsen

    (Norwegian University of Science and Technology)

  • Aytac Kadir Mutlu

    (Norwegian University of Science and Technology)

  • Ricarda Bardenhewer

    (Norwegian University of Science and Technology)

  • Suresh Kumar Jetti

    (Neuro-Electronics Research Flanders)

  • Stephan C. F. Neuhauss

    (Department of Molecular Life Sciences)

  • Nathalie Jurisch-Yaksi

    (Norwegian University of Science and Technology
    Norwegian University of Science and Technology)

  • Emre Yaksi

    (Norwegian University of Science and Technology
    Koç University School of Medicine)

Abstract

Inhibition plays a key role in brain functions. While typically linked to GABA, inhibition can be induced by glutamate via metabotropic glutamate receptors (mGluRs). Here, we investigated the role of mGluR-mediated inhibition in the habenula, a conserved, glutamatergic brain hub involved in adaptive and defensive behaviors. We found that zebrafish and mice habenula express group III mGluRs. We showed that group III mGluRs regulate membrane potential and calcium activity of zebrafish habenula. Perturbing group III mGluRs increased sensory-evoked excitation and reduced selectivity. We identified inhibition as the primary communication mode among habenula neurons. Blocking group III mGluRs reduces this inhibition and increases neural synchrony. Consistently, we demonstrated that multisensory integration in the habenula relies on competitive suppression, that partly depends on group III mGluRs. Genetic and pharmacological perturbation of group III mGluRs amplified neural responses and defensive behaviors. Our findings highlight an essential role for mGluR-driven inhibition in encoding information and regulating defensive behaviors.

Suggested Citation

  • Anna Maria Ostenrath & Nicholas Faturos & Yağnur Işık Çiftci Çobanoğlu & Bram Serneels & Inyoung Jeong & Ekin Dongel Dayanc & Anja Enz & Francisca Hinrichsen & Aytac Kadir Mutlu & Ricarda Bardenhewer , 2025. "Inhibition mediated by group III metabotropic glutamate receptors regulates habenula activity and defensive behaviors," Nature Communications, Nature, vol. 16(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62115-z
    DOI: 10.1038/s41467-025-62115-z
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