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Dopamine D1–D2 signalling in hippocampus arbitrates approach and avoidance

Author

Listed:
  • Arthur Godino

    (Icahn School of Medicine at Mount Sinai
    INMED)

  • Marine Salery

    (Icahn School of Medicine at Mount Sinai)

  • Angelica M. Minier-Toribio

    (Icahn School of Medicine at Mount Sinai)

  • Vishwendra Patel

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • John F. Fullard

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Veronika Kondev

    (Icahn School of Medicine at Mount Sinai)

  • Eric M. Parise

    (Icahn School of Medicine at Mount Sinai)

  • Freddyson J. Martinez-Rivera

    (Icahn School of Medicine at Mount Sinai)

  • Carole Morel

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Panos Roussos

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai
    James J. Peters VA Medical Center)

  • Robert D. Blitzer

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

  • Eric J. Nestler

    (Icahn School of Medicine at Mount Sinai
    Icahn School of Medicine at Mount Sinai)

Abstract

The hippocampus1–6, as well as dopamine circuits7–9, coordinates decision-making in anxiety-eliciting situations. Yet, little is known about how dopamine modulates hippocampal representations of emotionally salient stimuli to inform appropriate resolution of approach versus avoidance conflicts. Here we studied dopaminoceptive neurons in the male mouse ventral hippocampus (vHipp), molecularly distinguished by their expression of dopamine D1 or D2 receptors. We show that these neurons are transcriptionally distinct and topographically organized across vHipp subfields and cell types. In the ventral subiculum where they are enriched, both D1 and D2 neurons are recruited during anxiogenic exploration, yet with distinct profiles related to investigation and behavioural selection. In turn, they mediate opposite approach–avoidance responses, and are differentially modulated by dopaminergic transmission in that region. Together, these results suggest that vHipp dopamine dynamics gate exploratory behaviours under contextual uncertainty, implicating dopaminoception in the complex computation engaged in the vHipp to govern emotional states.

Suggested Citation

  • Arthur Godino & Marine Salery & Angelica M. Minier-Toribio & Vishwendra Patel & John F. Fullard & Veronika Kondev & Eric M. Parise & Freddyson J. Martinez-Rivera & Carole Morel & Panos Roussos & Rober, 2025. "Dopamine D1–D2 signalling in hippocampus arbitrates approach and avoidance," Nature, Nature, vol. 643(8071), pages 448-457, July.
  • Handle: RePEc:nat:nature:v:643:y:2025:i:8071:d:10.1038_s41586-025-08957-5
    DOI: 10.1038/s41586-025-08957-5
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