Rosanna P. Sammons, Mourat Vezir, Laura Moreno-Velasqueza, Gaspar Cano, Marta Orlando, Meike Sievers, Eleonora Grass, Verjinia D. Metodieva, Richard Kempter, Helene Schmidt and Dietmar Schmitz

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.

PNAS. 121 (6) e2312281120 (2024)