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

Overview

Authors: Victor Vargas-Barroso1, Jake F. Watson1, Andrea Navas-Olive1, Alois Schlögl1, Peter Jonas1
ORCID iDs: Victor Vargas-Barroso, Jake F. Watson, Andrea Navas-Olive, Alois Schlögl, Peter Jonas
  1. Institute of Science and Technology Austria (ISTA),Klosterneuburg, Austria
Institutions: Institute of Science and Technology Austria (Austria)
Journal: Nature communications, volume 17, issue 1, article 5540
Dates: received 3 September 2025; accepted 3 April 2026; published online 21 April 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41467-026-71914-x · PMID 42014695 · PMCID PMC13287488 · OpenAlex W7155104329
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: intracellular / patch clamp (modality), mouse (organism)
Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials
Keywords: Synaptic transmission, Development of the nervous system, Neural circuits, Computational neuroscience
MeSH: CA3 Region, Hippocampal*, Memory*, Nerve Net*, Pyramidal Cells*, Synapses*, Animals, Mice, Mice, Inbred C57BL, Neurodevelopment, Neuronal Plasticity, Patch-Clamp Techniques (* major topic)
Topic: Memory and Neural Mechanisms (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) (GIANTSYN 692692, CA3-SYNGRAM 101199096, Marie Sklodowska-Curie Grant 754411); Austrian Science Fund (P 36232-B, PAT4178023, 10.55776 / CoE16); EC | EU Framework Programme for Research and Innovation H2020 | H2020 Excellent Science (H2020 Priority Excellent Science) (Marie Sklodowska-Curie Grant 101026635); NOMIS Stiftung (NOMIS Foundation)
Citations: cited by 1 paper (Europe PMC); 88 references in the paper
Research resources: Wild-type C57BL/6J mice RRID:IMSR_JAX:000664

Abstract

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.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

research-explorer.ista.ac.at/download/21442

License: none: the authors keep all their rights
State: the link answers, verified on 29 September 2026
Evidence: the link answers
Software Heritage: not checked
Found in: “Code availability”
Not found: README, license file, CITATION.cff, environment file, tests, continuous integration, documentation
Availability: 1 check, the latest on 29 September 2026: the link answers (HTTP 200)
  • 29 September 2026: the link answers (HTTP 200)
At the source: research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz

Code availability

Code is available from 10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz.

Reproduced under the paper's license (CC BY), from the paper cited above.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

  • 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 0 scripts, each with its path and the digest of its content;
  • no match between paragraphs and code yet;
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Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

No dataset and no data link were found in the paper.

Data availability

Source data are provided with this paper. Additional original data are available from the corresponding author upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 29 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 4 keywords, 11 MeSH terms, 4 funders, 86 references, 1 RRID.

Cite

This paper

Vargas-Barroso, V., Watson, J. F., Navas-Olive, A., Schlögl, A., & Jonas, P. (2026). Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit. Nature communications, 17(1), 5540. https://doi.org/10.1038/s41467-026-71914-x

BibTeX

@article{vargasbarroso2026developmental,
author = {Vargas-Barroso, Victor and Watson, Jake F. and Navas-Olive, Andrea and Schlögl, Alois and Jonas, Peter},
title = {{Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit}},
journal = {Nature communications},
year = {2026},
month = apr,
volume = {17},
number = {1},
pages = {5540},
publisher = {Nature Publishing Group},
issn = {2041-1723},
doi = {10.1038/s41467-026-71914-x},
url = {https://doi.org/10.1038/s41467-026-71914-x},
pmid = {42014695},
pmcid = {PMC13287488}
}

RIS

TY - JOUR
AU - Vargas-Barroso, Victor
AU - Watson, Jake F.
AU - Navas-Olive, Andrea
AU - Schlögl, Alois
AU - Jonas, Peter
TI - Developmental emergence of sparse and structured synaptic connectivity in the hippocampal CA3 memory circuit
T2 - Nature communications
J2 - Nat Commun
PY - 2026
DA - 2026/04/21
VL - 17
IS - 1
SP - 5540
SN - 2041-1723
PB - Nature Publishing Group
DO - 10.1038/s41467-026-71914-x
UR - https://doi.org/10.1038/s41467-026-71914-x
LA - en
ER -

CSL-JSON

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