Generality and opponency of rostromedial tegmental (RMTg) roles in valence processing

The rostromedial tegmental nucleus (RMTg), a GABAergic afferent to midbrain dopamine (DA) neurons, has been hypothesized to encode aversive stimuli. However, this encoding pattern has only been demonstrated for a limited number of stimuli, and its influence on the ventral tegmental (VTA) responses to aversive stimuli is untested. Here, we found that RMTg neurons show average inhibitions to rewarding stimuli and excitations to aversive stimuli of greatly varying sensory modalities and timescales. Notably, negative valence-encoding neurons are particularly enriched in subpopulations projecting to the VTA versus other targets. Additionally, RMTg neurons also dynamically encode \"opponent\" changes in motivational states induced by removal of sustained stimuli. Finally, excitotoxic RMTg lesions impair conditioned place aversion to multiple aversive stimuli, and greatly reduce aversive stimulus-induced inhibitions in VTA neurons, particularly in putative DA-like neurons. Together, our findings indicate a broad RMTg role in encoding aversion and potentially driving DA responses and behavior.