Structure and function of the hippocampal CA3 module

Author:

Sammons Rosanna P.1ORCID,Vezir Mourat2,Moreno-Velasquez Laura1ORCID,Cano Gaspar3ORCID,Orlando Marta1ORCID,Sievers Meike4,Grasso Eleonora2ORCID,Metodieva Verjinia D.1ORCID,Kempter Richard356ORCID,Schmidt Helene2,Schmitz Dietmar15678ORCID

Affiliation:

1. Neuroscience Research Center, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Neuroscience Research Center, Berlin 10117, Germany

2. Ernst Strüngmann Institute for Neuroscience, Frankfurt am Main 60528, Germany

3. Institute for Theoretical Biology, Department of Biology, Humboldt-Universität zu Berlin, Berlin 10115, Germany

4. Department of Connectomics, Max Planck Institute for Brain Research, Frankfurt am Main 60438, Germany

5. Bernstein Center for Computational Neuroscience Berlin, Berlin 10115, Germany

6. Einstein Center for Neurosciences Berlin, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin and Berlin Institute of Health, Einstein Center for Neurosciences Berlin, Berlin 10117, Germany

7. German Center for Neurodegenerative Diseases Berlin, Berlin 10117, Germany

8. Max-Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin 13125, Germany

Abstract

The hippocampal formation is crucial for learning and memory, with submodule CA3 thought to be the substrate of pattern completion. However, the underlying synaptic and computational mechanisms of this network are not well understood. Here, we perform circuit reconstruction of a CA3 module using three dimensional (3D) electron microscopy data and combine this with functional connectivity recordings and computational simulations to determine possible CA3 network mechanisms. Direct measurements of connectivity schemes with both physiological measurements and structural 3D EM revealed a high connectivity rate, multi-fold higher than previously assumed. Mathematical modelling indicated that such CA3 networks can robustly generate pattern completion and replay memory sequences. In conclusion, our data demonstrate that the connectivity scheme of the hippocampal submodule is well suited for efficient memory storage and retrieval.

Funder

Deutsche Forschungsgemeinschaft

EC | ERC | HORIZON EUROPE European Research Council

Bundesministerium für Bildung und Forschung

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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4. Computational constraints suggest the need for two distinct input systems to the hippocampal CA3 network

5. Computational analysis of the role of the hippocampus in memory

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