SUSTAINED DOPAMINERGIC PLATEAUS AND NORADRENERGIC DEPRESSIONS BIAS TRANSITIONS INTO EXPLOITATIVE BEHAVIORAL STATES

Abstract

We are constantly faced with the trade-off between exploiting actions with known outcomes and exploring alternative actions whose outcomes may be better. This balance has been hypothesized to rely on dopaminergic neurons of the substantia nigra pars compacta (SNc)1 and noradrenergic neurons of the locus coeruleus (LC)2-3. We developed a behavioral paradigm to capture exploitative and exploratory states, and imaged calcium dynamics in genetically-identified dopaminergic SNc neurons and noradrenergic LC neurons during state transitions. During exploitative states, characterized by motivated repetition of the same action choice, we found dichotomous changes in baseline activity in SNc and LC, with SNc showing higher and LC showing lower sustained activity. These sustained neural states emerged from the accumulation of lengthened positive responses and hysteretic dynamics in SNc networks, and lengthened negative responses in LC. Sustained activity could not be explained by classical reinforcement learning parameters, and in SNc but not LC, emerged in subpopulations coding for response vigor. Manipulating the sustained activity of SNc and LC revealed that dopaminergic activity primarily mediates engagement and motivation, whereas noradrenergic activity modulates action selection. These data uncover the emergence of sustained neural states in dopaminergic and noradrenergic networks that mediate dissociable aspects of exploitative bouts.