Excitatory VTA to DH projections provide a valence signal to memory circuits

The positive or negative value (valence) of past experiences is normally integrated into neuronal circuits that encode episodic memories and plays an important role in guiding behavior. Here, we show, using mouse behavioral models, that glutamatergic afferents from the ventral tegmental area to the dorsal hippocampus (VTA -> DH) signal negative valence to memory circuits, leading to the formation of fear-inducing context memories and to context-specific reinstatement of fear. To a lesser extent, these projections also contributed to opioid-induced place preference, suggesting a role in signaling positive valence as well, and thus a lack of dedicated polarity. Manipulations of VTA terminal activity were more effective in females and paralleled by sex differences in glutamatergic signaling. By prioritizing retrieval of negative and positive over neutral memories, the VTA -> DH circuit can facilitate the selection of adaptive behaviors when current and past experiences are valence congruent. The neuronal pathway that signals the positive or negative value of memories is not well understood. Here, the authors report that an excitatory projection from the ventral tegmental area to the dorsal hippocampus carries the valence information, contributing, especially in females, to the recurrence of fear and to drug seeking behavior.