Inactivation of ventral hippocampus projections promotes sensitivity to changes in contingency.

The loss of behavioral flexibility is common across a number of neuropsychiatric illnesses. This may be in part due to the loss of the ability to detect or use changes in action-outcome contingencies to guide behavior. There is growing evidence that the ventral hippocampus plays a critical role in the regulation of flexible behavior and reward-related decision making. Here, we investigated the role of glutamatergic projections from the ventral hippocampus in the expression of contingency-mediated reward seeking. We demonstrate that selectively silencing ventral hippocampus projections can restore the use of action-outcome contingencies to guide behavior, while sparing cue-guided behavior and extinction learning. Our findings further indicated that the ability of the ventral hippocampus to promote habitual response strategies may be in part mediated by selective projections from the ventral hippocampus to the nucleus accumbens shell. Together these results implicate glutamatergic projections from the ventral hippocampus in the regulation of behavioral flexibility and suggest that alterations in ventral hippocampus function may contribute to overreliance on habitual response strategy observed in neuropsychiatric illnesses including addiction and obsessive-compulsive disorder.