Dopamine D1-D2 signalling in hippocampus arbitrates approach and avoidance

Abstract

The hippocampus^1-6, as well as dopamine circuits^7-9, 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.