---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
PlanS_conform: '1'
_id: '22229'
abstract:
- lang: eng
text: 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.
acknowledged_ssus:
- _id: PreCl
- _id: Bio
- _id: M-Shop
- _id: ScienComp
acknowledgement: 'We thank Jose Guzman, Simon Hippenmeyer, and Tim Vogels for critically
reading the manuscript, Jozsef Csicsvari for useful discussions, Florian Marr for
technical assistance, and Eleftheria Kralli-Beller for manuscript editing. This
research was supported by the Scientific Services Units (SSUs) of ISTA: the preclinical
facility (PCF) provided housing and breeding of the animals, the imaging and optics
facility (IOF) offered technical training and state of the art equipment, the Miba
machine shop contributed to the construction and maintenance of multicellular recording
setups, and the scientific computing unit helped with the large-scale simulations.
The project received funding from the European Union’s Horizon 2020 research and
innovation programme (ERC Advanced Grants No 692692 GIANTSYN and 101199096 CA3-SYNGRAM
to P.J.; Marie Skłodowska-Curie Grant 754411 to V.V.B.; Marie Skłodowska-Curie Grant
101026635 to J.F.W.), the Fond zur Förderung der Wissenschaftlichen Forschung (P
36232-B, PAT4178023, and 10.55776/CoE16 to P.J.), and the Nomis Foundation (fellowship
to A.N.-O.). V.V.B. received funding from a CONACyT fellowship (289638).'
article_number: '5540'
article_processing_charge: Yes
article_type: original
author:
- first_name: Victor M
full_name: Vargas Barroso, Victor M
id: 2F55A9DE-F248-11E8-B48F-1D18A9856A87
last_name: Vargas Barroso
- first_name: Jake
full_name: Watson, Jake
id: 63836096-4690-11EA-BD4E-32803DDC885E
last_name: Watson
orcid: 0000-0002-8698-3823
- first_name: Andrea C
full_name: Navas Olivé, Andrea C
id: 739d26c9-52e8-11ee-8d72-f14d3893b4ce
last_name: Navas Olivé
orcid: 0000-0002-9280-8597
- first_name: Alois
full_name: Schlögl, Alois
id: 45BF87EE-F248-11E8-B48F-1D18A9856A87
last_name: Schlögl
orcid: 0000-0002-5621-8100
- first_name: Peter M
full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
last_name: Jonas
orcid: 0000-0001-5001-4804
citation:
ama: 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:10.1038/s41467-026-71914-x
apa: 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. https://doi.org/10.1038/s41467-026-71914-x
chicago: 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. https://doi.org/10.1038/s41467-026-71914-x.
ieee: 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.
ista: 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.
mla: 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:10.1038/s41467-026-71914-x.
short: V.M. Vargas Barroso, J. Watson, A.C. Navas Olivé, A. Schlögl, P.M. Jonas,
Nature Communications 17 (2026).
corr_author: '1'
das_tickbox: '1'
dataavailabilitystatement: Source data are provided with this paper. Additional original
data are available from the corresponding author upon request. Code is available
from https://doi.org/10.15479/AT-ISTA-21442 under the link https://research-explorer.ista.ac.at/download/21442/21443/ca3simu-vargas2026v1.tar.gz
date_created: 2026-06-30T13:05:52Z
date_published: 2026-06-23T00:00:00Z
date_updated: 2026-07-01T06:47:49Z
day: '23'
ddc:
- '570'
department:
- _id: PeJo
- _id: ScienComp
doi: 10.1038/s41467-026-71914-x
ec_funded: 1
external_id:
pmid:
- '42014695'
file:
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checksum: d0b0093493926985b4c268662ff4d556
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creator: dernst
date_created: 2026-07-01T06:46:06Z
date_updated: 2026-07-01T06:46:06Z
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file_size: 18304997
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file_date_updated: 2026-07-01T06:46:06Z
has_accepted_license: '1'
intvolume: ' 17'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '06'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 25B7EB9E-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
- _id: e62b56fe-ab3c-11f0-94c7-d181dd352b3b
grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: bd88be38-d553-11ed-ba76-81d5a70a6ef5
grant_number: P36232
name: Mechanisms of GABA release in hippocampal circuits
- _id: 8d9195e9-16d5-11f0-9cad-d075be887a1e
grant_number: PAT 4178023
name: Synaptic networks of human brain
- _id: 26366136-B435-11E9-9278-68D0E5697425
name: Reglas de Conectividad funcional en el hipocampo
publication: Nature Communications
publication_identifier:
eissn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
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relation: research_data
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researchdata_availability: yes
scopus_import: '1'
status: public
supplementarymaterial: yes
title: Developmental emergence of sparse and structured synaptic connectivity in the
hippocampal CA3 memory circuit
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 17
year: '2026'
...