Brain-wide connectivity and novelty response of the dorsal endopiriform nucleus in mice

The dorsal endopiriform nucleus (EPd) is a cortical subplate structure within the piriform cortex that shares similar developmental origins to those of the claustrum. Although implicated in epilepsy and olfaction, the EPd's connectivity and function remain largely unclear due to the lack of specific molecular markers. Our recent mapping study identifies the oxytocin receptor (Oxtr) as highly enriched in the EPd. Immunohistochemical and spatial transcriptomic analyses confirm Oxtr enrichment and a distinct molecular profile of the EPd compared to the claustrum. Whole-brain input-output mapping of EPd-Oxtr neurons unveils extensive bidirectional connections with ventral brain regions, orchestrating circuits regulating olfaction, internal state, and emotion. Furthermore, in vivo miniscope recordings reveal that EPd-Oxtr neurons exhibit high baseline activity during exploration, with a sharp decrease in response to novel stimuli. Together, these findings suggest that EPd-Oxtr neurons integrate interoceptive and exteroceptive signals, contributing to internal state regulation and behavioral adaptation to novel environmental cues.