The mouse dorsal peduncular cortex encodes fear memory.

The rodent medial prefrontal cortex (mPFC) is functionally organized across the dorsoventral axis, where dorsal and ventral subregions promote and suppress fear, respectively. As the ventral-most subregion, the dorsal peduncular cortex (DP) is hypothesized to function in fear suppression. However, this role has not been explicitly tested. Here, we demonstrate that the DP paradoxically functions as a fear-encoding brain region and plays a minimal role in fear suppression. By using multimodal analyses, we demonstrate that DP neurons exhibit fear-learning-related plasticity and acquire cue-associated activity across learning and memory retrieval and that DP neurons activated by fear memory acquisition are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of DP fear-related neural ensembles drive the promotion and suppression of freezing, respectively. Overall, our results suggest that the DP plays a role in fear memory encoding. Moreover, our findings redefine our understanding of the functional organization of the rodent mPFC.

The mouse dorsal peduncular cortex encodes fear memory.

The rodent medial prefrontal cortex (mPFC) is a locus for both the promotion and suppression (e.g. extinction) of fear and is composed of four anatomically distinct subregions, including anterior cingulate 1 (Cg1), prelimbic (PL), infralimbic (IL), and the dorsal peduncular (DP) cortex. A vast majority of studies have focused on Cg1, PL, and IL. The Cg1 and PL have been implicated in the promotion of fear, while the IL has been linked to a role in the suppression, or extinction, of fear. Due to its anatomical location ventral to IL, the DP has been hypothesized to function as a fear-suppressing brain region however, no studies have explicitly tested its role in this function or in the regulation of memory generally. Moreover, some studies have pointed towards a dichotomous role for ventral mPFC in the dual suppression and promotion of fear, but the mechanisms underlying these opposing observations remains unclear. Here, we provide evidence that the DP paradoxically functions as a cued fear-encoding brain region and plays little to no role in fear memory extinction. By using a combination of cFos immunohistochemistry, whole-cell brain slice electrophysiology, fiber photometry, and activity-dependent neural tagging, we demonstrate that DP neurons exhibit learning-related plasticity, acquire cue-associated activity across learning and memory retrieval, and that DP neurons activated by learning are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of fear learning-related DP neural ensembles drives the promotion and suppression of freezing, respectively. Overall, these data suggest that the DP plays an unexpected role in fear memory encoding. More broadly, our results reveal new principles of organization across the dorsoventral axis of the mPFC.