Dynamical management of potential threats regulated by dopamine and direct- and indirect-pathway neurons in the tail of the striatum

Avoiding potential threats before experiencing an actual outcome is critical to prevent a disaster. Here we examined roles of the tail of the striatum (TS) and its dopamine input in threat management. Mice were presented with a potential threat (a moving object) while pursuing rewards. Mice initially failed to obtain rewards, but gradually successfully obtained rewards in later trials. We show that the initial failures depended on dopamine and direct-pathway neurons in TS, and variability in failure rate across trials and individuals was positively correlated with the activity of these neurons. In contrast, indirect-pathway neurons in TS were critical for eventual improvement in reward acquisition, and their activity was positively correlated with successful reward acquisition. These results demonstrate that direct- and indirect-pathway TS neurons promote and suppress threat avoidance, respectively, at different stages, providing a mechanism for overcoming a potential threat while maintaining the threat estimates.