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bioRxiv · 10.64898/2026.11.01.763440

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

MacLaren, D. A. A.·Saidov, K. M.·Schlesiger, M. I.·Monyer, H.
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Abstract

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.

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MacLaren, D. A. A., Saidov, K. M., Schlesiger, M. I., Monyer, H.. 2026-11-03. Distinct medial septal GABAergic pathways differentially regulate spatial memory and network activity. https://doi.org/10.64898/2026.11.01.763440

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