Distinct medial septal GABAergic pathways differentially regulate spatial memory and network activity

Septal GABAergic projection neurons form distinct pathways to subregions of the hippocampal formation, including the hippocampus proper and the medial and lateral entorhinal cortices. Parvalbumin (PV+) and calbindin expressing (CB+) projections target different types of interneurons and thereby differentially regulate neuronal activity in the downstream area. Consistent with the idea of dissociable functional roles, inhibition of septal PV+ neurons impairs reference memory whereas inhibition of septal CB+ neurons impairs both reference and working memory. Here, we show that these functions are differentially supported by specific projection pathways: PV+ projections to the dorsal hippocampus and medial entorhinal cortex (MEC) support reference memory, whereas CB+ projections to the MEC support both reference and working memory. At the network level, septal PV+, but not CB+, neurons regulate theta oscillations. Together, these findings further define the roles of septal PV+ and CB+ pathways in orchestrating network activity and supporting specific forms of memory.