REPRESENTATION OF MULTIPLE REWARDING AND AVERSIVE STIMULI IN THE ROSTROMEDIAL TEGMENTAL NUCLEUS

The rostromedial tegmental nucleus (RMTg) is the main inhibitory input to the midbrain dopaminergic system. It is implicated in aversive information processing, however, its relevance in reward processing is less understood. Importantly, the degree of heterogeneity in encoding distinct rewards, and the overlap between these representations at the single-cell level, remain unresolved.
We recorded the activity of RMTg neurons in freely-behaving male mice using Neuropixels probes while animals spontaneously explored multiple rewards: water, food, a novel object, a shelter, and a freely-moving female conspecific; animals were also exposed to aversive stimuli.
Aversive stimuli excited most RMTg cells; exploratory behaviors elicited excitations, whereas consummatory ones, including eating, drinking, and sexual behaviour, produced inhibition. Population analysis revealed pronounced heterogeneity: responses to food and water were congruent across neurons, while aversive responses were orthogonal to other stimuli. Similarly, dimensionality reduction showed that eating followed population trajectories distinct from those associated with sexual and aversive stimuli. Unsupervised clustering showed that most neurons are inhibited by consummatory behaviors and excited by aversion. Notably, individual stimuli could be reliably decoded from ensemble neuronal activity. Moreover, successful mating trials, unlike failed attempts, elicited inhibition of RMTg neurons; pre-ejaculation but not post-ejaculation sniffing excited RMTg neurons. Further, we identified neurons exhibiting rhythmic activity locked to thrusting movements.
Together, these findings reveal a heterogeneous yet structured organization of RMTg reward encoding, positioning it as a dynamic integrator of multiple rewarding and aversive stimuli rather than a purely aversion-regulating brain region.
We acknowledge funding by DFG, EXC2030-CECAD (to TK).