Sammons, R. P., Vezir, M., Moreno-Velasquez, L., Cano, G., Orlando, M., Sievers, M., … & Schmitz, D. (2024). Structure and function of the hippocampal CA3 module. Proceedings of the National Academy of Sciences, 121(6), e2312281120. https://www.pnas.org/doi/abs/10.1073/pnas.2312281120
Volume electron microscopy and simultaneous whole-cell recordings of up to eight neurons
Mouse hippocampus CA3
Autoassociative models of how CA3 stores memories typically assume a high degree of recurrent connectivity. This paper quantifies that connectivity. The authors acquired a large (965 x 808 x 62 micron) volume electron microscopy dataset spanning all layers of CA3. Since this volume is thin in one direction, they first identified seven pyramidal neurons with at least two axon collaterals in the volume and reconstructed their entire axonal arbors throughout the volume. They identified all synapses these axons made onto other pyramidal neurons. Using this data, they calculated the probability of such recurrent synapses as a function of inter-somatic distance. They found a local connectivity probability of 11% within 50 microns that dropped to 5.5% within 250 microns. In a separate experiment, the authors performed simultaneous whole-cell recordings of up to eight CA3 neurons in 119 acute mouse hippocampal slices (400 microns thick). They found a probability of synaptic connection of 8.8% which was in line with their EM results. Finally the authors performed computational modeling showing that this relatively high recurrent connectivity supports pattern completion in a spiking model of CA3 memory encoding.
“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.”
