Firing rate suppression of the medial septum during spatial working memory maintenance without navigation

The medial septum (MS) was shown to participate in working memory (WM) processes: MS lesions led to deficits in spatial WM performance, and hippocampal theta oscillations, known to depend on the MS, were linked to WM maintenance. However, what activity features of the MS may support working memory has not been explored. Therefore, we directly compared MS single neuron activity in mice performing a 2-alternative forced choice task with and without a WM component.

Importantly, we minimized the locomotion component of the task to dissociate spatial navigation and WM processes. We found that the dominant response during stimulus processing and the subsequent delay period was a suppression of activity. WM engagement was characterized by stronger responsiveness of MS neurons compared to control, and especially a stronger firing rate suppression in the second half of the delay period.

Moreover, we found fewer strongly theta-rhythmic neurons in the MS during WM performance, and these neurons were more suppressed during the delay period when WM was engaged. Based on these results, the MS may have an enabling rather than an active role in hippocampal WM processing. We thank Katalin Lengyel for technical assistance in anatomical methods.

We thank the FENS-Kavli Network of Excellence for fruitful discussions. This work was supported by the Hungarian Brain Research Program NAP3.0 (NAP2022-I-1/2022) of the Hungarian Academy of Sciences, the “Lendület” LP2024-8/2024 grant by the Hungarian Academy of Sciences, the NKFIH K147097 grant of the National Research, Development and Innovation Office and the European Union project RRF-2.3.1-21-2022-00004 within the framework of the Artificial Intelligence National Laboratory. Malek Aouadi and Nicola Solari contributed equally to this work.

MTA–HUN-REN KOKI Lendület “Momentum” Laboratory of Systems Neuroscience, HUN-REN Institute of Experimental Medicine, Budapest, 1083, Hungary Malek Aouadi, Nicola Solari, Johanna Petra Szabó, Bálint Király & Balázs Hangya János Szentágothai Neurosciences Program, Semmelweis University School of PhD Studies, Budapest, 1085, Hungary Subcortical Modulation Research Group, HUN-REN Institute of Experimental Medicine, Budapest, 1083, Hungary Epilepsy Center, Institute of Neurosurgery and Neurointervention, Semmelweis University, Budapest, 1085, Hungary Division of Neurophysiology, Center for Brain Research, Medical University of Vienna, 1090, Vienna, Austria The authors declare no competing interests. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Below is the link to the electronic supplementary material.

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