Dopamine D1–D2 signalling in hippocampus arbitrates approach and avoidance

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, Robert D. Blitzer and Eric J. Nestler ()
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Arthur Godino: Icahn School of Medicine at Mount Sinai
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
John F. Fullard: 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
Panos Roussos: Icahn School of Medicine at Mount Sinai
Robert D. Blitzer: Icahn School of Medicine at Mount Sinai
Eric J. Nestler: Icahn School of Medicine at Mount Sinai

Nature, 2025, vol. 643, issue 8071, 448-457

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41586-025-08957-5

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