Rules of disengagement: orexin-arousal and dopamine-utility as separable axes

In mice performing a shifting-reward decision task, pupil-linked arousal and dopaminergic utility coding predict engagement-state transitions along separable axes, including distinct drug effects.

• Why it matters: The neural mechanisms that govern staying engaged, disengaging, and returning to tasks—linked to utility and arousal—remain unclear.
• What they did: Using a decision-making task with shifting reward size, the study inferred latent engagement states and tested how almorexant and semaglutide altered transitions, using pupil-linked arousal and dopamine signals.
• The result: Orexin antagonism with almorexant disengaged mice at low reward via pupil-linked arousal rather than dopamine, while semaglutide reduced the gain of accumbal dopamine’s reward-history integration, predicting progressive disengagement without detectable arousal or orexin contribution.

AI summary of the abstract · may contain errors · not medical advice · read the paper.