Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit

article Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit published yes Victor M Vargas Barroso author 2F55A9DE-F248-11E8-B48F-1D18A9856A87 Jake Watson author 63836096-4690-11EA-BD4E-32803DDC885E0000-0002-8698-3823 Andrea C Navas Olivé author 739d26c9-52e8-11ee-8d72-f14d3893b4ce0000-0002-9280-8597 Alois Schlögl author 45BF87EE-F248-11E8-B48F-1D18A9856A870000-0002-5621-8100 Peter M Jonas author 353C1B58-F248-11E8-B48F-1D18A9856A870000-0001-5001-4804 PeJo department ScienComp department Biophysics and circuit function of a giant cortical glutamatergic synapse project Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits project ISTplus - Postdoctoral Fellowships project Synaptic computations of the hippocampal CA3 circuitry project Mechanisms of GABA release in hippocampal circuits project Synaptic networks of human brain project Reglas de Conectividad funcional en el hipocampo project Hippocampal CA3 pyramidal neurons (PNs) form the largest autoassociative network in the mammalian brain. Whether CA3–CA3 recurrent connectivity is genetically preconfigured or environmentally shaped during ongoing memory storage is currently unknown. To address this question, we performed multicellular patch-clamp-based circuit mapping of up to eight CA3 PNs in the mouse hippocampus at multiple postnatal time points (P7–8, P18–25, and P45–50). Here, we show that the hippocampal CA3 network undergoes a developmental transformation from local, dense, and random connectivity to a distributed, sparse, and structured configuration. Thus, sparse and structured connectivity may emerge via experience-dependent mechanisms. In parallel, the strength of single synapses is downregulated; single synaptic events are sufficient to trigger postsynaptic spiking early in development, whereas spatial summation of several inputs is required at later time points. Biologically inspired models of memory storage by Hebbian synaptic plasticity and retrieval via pattern completion suggest that developmental changes improve specific aspects of memory storage and retrieval. Our results imply a developmental transformation of the neuronal code and the memory functions in the hippocampal CA3 network. https://research-explorer.ista.ac.at/download/22229/22231/2026_NatureComm_VargasBarroso.pdf application/pdfno Springer Nature2026 eng Nature Communications 2041-1723 4201469510.1038/s41467-026-71914-x 17 https://research-explorer.ista.ac.at/record/21442 V. M. Vargas Barroso, J. Watson, A. C. Navas Olivé, A. Schlögl, and P. M. Jonas, “Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit,” Nature Communications, vol. 17. Springer Nature, 2026. Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature Communications. 2026;17. doi:<a href="https://doi.org/10.1038/s41467-026-71914-x">10.1038/s41467-026-71914-x</a> Vargas Barroso, V. M., Watson, J., Navas Olivé, A. C., Schlögl, A., & Jonas, P. M. (2026). Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature Communications. Springer Nature. <a href="https://doi.org/10.1038/s41467-026-71914-x">https://doi.org/10.1038/s41467-026-71914-x</a> Vargas Barroso, Victor M, Jake Watson, Andrea C Navas Olivé, Alois Schlögl, and Peter M Jonas. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” Nature Communications. Springer Nature, 2026. <a href="https://doi.org/10.1038/s41467-026-71914-x">https://doi.org/10.1038/s41467-026-71914-x</a>. Vargas Barroso, Victor M., et al. “Developmental Emergence of Sparse and Structured Synaptic Connectivity in the Hippocampal CA3 Memory Circuit.” Nature Communications, vol. 17, 5540, Springer Nature, 2026, doi:<a href="https://doi.org/10.1038/s41467-026-71914-x">10.1038/s41467-026-71914-x</a>. Vargas Barroso VM, Watson J, Navas Olivé AC, Schlögl A, Jonas PM. 2026. Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature Communications. 17, 5540. V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas, Nature Communications 17 (2026). 222292026-06-30T13:05:52Z2026-07-01T06:47:49Z