Endopiriform neurons projecting to ventral CA1 are a critical node for recognition memory

The claustrum complex is viewed as fundamental for higher order cognition; however, the circuit organization and function of its ventral subregion, the endopiriform (EN), are not well understood. Using circuit analyses in mice, we show that EN neurons defined by their projection to ventral CA1 (EN ^vCA1-proj. neurons) were a major source of afferents to ventral CA1 (vCA1), with diverging collaterals to the olfactory-limbic system, and formed recurrent circuits within EN and with the piriform cortex. In vCA1, these axons exclusively targeted the distal subregion triggering potent feedforward inhibition of pyramidal neurons. By combining in vivo neuronal activity monitoring, circuit manipulations, and behavior analysis, we found that, during all phases of recognition memory test, the EN ^vCA1-proj. activity correlated with the time mice spent in particular arena locations. The EN ^vCA1-proj. activity was biased around social or non-social stimuli when they were present, especially when they were novel, a pattern consistent with salience detection and attention. Inhibition of EN ^vCA1-proj. neurons disrupted mice’s memory-guided response to novel relative to familiar stimuli, without affecting innate bias for novel stimuli. These findings suggest EN as an essential node for social and object recognition memory, most likely by responding to salient environmental stimuli and by coordinating this response with downstream limbic system.