Striatal and hippocampal contributions to instrumental learning in the mouse using high-resolution behavioral monitoring and fMRI

The mammalian brain orchestrates goal-directed behavior through complex interactions between multiple memory systems, with the striatum and hippocampus playing pivotal interrelated roles. A central open question is the extent to which distinct memory signals from these systems drive learning to achieve desired goals and, once those are learned, maintain performance. Here, we used an MRI-compatible platform to obtain whole-brain functional imaging of head-fixed mice as they learn to perform a lick go/no-go odor discrimination task from the naïve state to task proficiency. Behaving mouse functional MRI (fMRI) acquired over a period of several days allowed us to characterize distributed activity as the animals learned the task, demonstrating differential involvement of the striatal and hippocampal memory systems accounting for correct and incorrect task responses. A consideration of the contribution of striatal sub-regions revealed that the responses of the dorsal striatum were correlated with improvement in reaction time, while responses in the ventral striatum were correlated with learning the task and maintaining task performance. In contrast, the dorsal hippocampus showed depressed responses to correct licks to the target odor (hits) and increased responses to incorrect licks to the non-target odor (false alarms). False alarms that were correlated with positive hippocampal responses had longer reaction times and emerged after the mouse learned the task, implicating the hippocampus in driving false memory responses. These results show that behaviorally beneficial actions were correlated with the striatum with a competing involvement of the hippocampus driving erroneous actions, setting the stage to study circuit-based mechanisms of false memory in the mouse.