Tachykinin 1-expressing neurons in the lateral habenula signal negative reward prediction error.

Evaluating outcomes to accurately predict which actions lead to reward is crucial for survival. Discrepancies between expected and realized outcomes, termed reward prediction errors (RPEs), serve as a teaching signal to update subsequent predictions and promote adaptive behavior. Neural correlates of RPEs have been identified in several brain regions, including the lateral habenula (LHb), which contains a subpopulation of neurons encoding negative reward prediction error (nRPE) that are excited by worse-than-expected outcomes and inhibited by better-than-expected outcomes. LHb projections to the midbrain shape firing in dopaminergic neurons and play a well-established role in reward learning and decision-making. However, the LHb engages in a wide variety of behaviors beyond reward processing, and it remains unclear whether these diverse functions are mediated by specific transcriptionally defined cell types. Little is known about the transcriptomic identity of nRPE-encoding neurons, limiting our understanding of the specific role of these signals in outcome valuation. Using cell type-specific recording in mice performing reward-guided tasks, we demonstrate neurons expressing the neuropeptide gene