Dorsal hippocampus‐ and ACC‐projecting medial septum neurons differentially contribute to the recollection of episodic‐like memory

Episodic memory refers to the recollection of previous experiences containing specific temporal, spatial, and emotional information. The ability to recollect episodic memory requires coordination of multiple brain regions, including the hippocampus (HPC) and the cingulate cortex. While the afferents into HPC and cingulate cortex that orchestrate the episodic memory remain unclear. The medial septum (MS), one of the anatomical location of cholinergic centers, innervates not only the dorsal HPC (dHPC), but also the cingulate and entorhinal cortices. By using “What‐Where‐When” episodic‐like memory (ELM) behavioral model and viral tracing, we found that MS neurons projected to dHPC and anterior cingulate cortex (ACC), which exerted distinct impacts on ELM recollection. Chemogenetic inhibition of the dHPC‐projecting MS neurons disrupted “What‐Where‐When” ELM recollection as well as object location, object‐in‐place, and recency recognition memories recollection, while chemogenetic inhibition of the ACC‐projecting MS neurons only disrupted “What‐Where‐When” ELM recollection. Moreover, neither dHPC‐ nor ACC‐projecting MS neurons were involved in novel object recognition memory recollection or locomotor activity. Immunostaining showed that ACC‐ and dHPC‐projecting MS neurons are partially overlapped populations. These findings reveal an unsuspected division of ELM processing and provide the potential mechanism that the recollection of episodic memory need the coordination of MS neurons projecting to dHPC and ACC.