Investigating context-dependent activity in dopamine neurons projecting to ventral striatum and tail of the striatum

Abstract

Adaptive behavior requires a careful balance between approaching rewarding stimuli and avoiding threatening stimuli. Midbrain dopamine neurons play a role in both processes, but exactly which subpopulations of dopamine neurons are responsible for reward approach vs. threat avoidance behavior – and how fixed these divisions are – remains to be fully clarified. In the present study, we test the boundaries of the commonly recognized roles of two dopamine subpopulations, those projecting to the ventral striatum (VS) and tail of the striatum (TS), in reward approach and threat avoidance behavior. In chapter 2, we investigate the role of VS-projecting dopamine neurons in a naturalistic reward-foraging task and characterize how this role changes with the introduction of a potential threat. We find that the introduction of the threat starkly changes the relationship between VS dopamine activity and the mouse’s behavior, observing that in the absence of threat, VS dopamine activity correlates with velocity as animals approach a reward; but in the conflicting presence of threat, VS dopamine activity correlates with velocity as animals escape to a shelter. Lesion studies confirm that VS-projecting dopamine neurons are important for both reward approach in the absence of threat, and escape to safety once a threat is introduced. Based on these findings, we propose that VS dopamine is involved in allocentric spatial navigation, potentially through facilitating the formation of a spatial value map. This role may complement the function of TS-projecting dopamine neurons in escape behavior, as past studies point to a role for this subpopulation in egocentric threat avoidance. In chapter 4, we investigate the role of TS-projecting dopamine neurons in a structured sensory discrimination task. We find that TS-projecting dopamine neurons encode contralateral choices made during reward-guided sensory discrimination, in a manner that does not align with current theories of TS dopamine function. Taken together, this body of work demonstrates the importance of considering the functional role of dopamine neuron subpopulations across varied contexts, to understand the full range of their impact on behavior.