---
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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
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Technology Austria. https://doi.org/10.15479/AT-ISTA-21442
chicago: Schlögl, Alois. “CA3Simu v1.06 (Vargas2026v1).” Institute of Science and
Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-21442.
ieee: A. Schlögl, “CA3Simu v1.06 (vargas2026v1).” Institute of Science and Technology
Austria, 2026.
ista: Schlögl A. 2026. CA3Simu v1.06 (vargas2026v1), Institute of Science and Technology
Austria, 10.15479/AT-ISTA-21442.
mla: Schlögl, Alois. CA3Simu v1.06 (Vargas2026v1). Institute of Science and
Technology Austria, 2026, doi:10.15479/AT-ISTA-21442.
short: A. Schlögl, (2026).
corr_author: '1'
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- ca3 simulations
- modelling
license: https://opensource.org/licenses/GPL-3.0
month: '03'
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grant_number: '101199096'
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name: Biophysics and circuit function of a giant cortical glutamatergic synapse
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acknowledged_ssus:
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acknowledgement: "This project was supported by the following funding agencies: ERC
under the European\r\nUnion's Horizon 2020 research and innovation program (ERC
Advanced Grants No 692692\r\n“GIANTSYN” and 101199096 “CA3-SYNGRAM” to P.J.), the
Fonds zur Förderung der\r\nwissenschaftlichen Forschung (P 36232-B, stand-alone
grant, PAT 4178023, principal\r\ninvestigator project, and 10.55776/CoE 16 “GABA
neurons” to P.J.), and the European Union’s\r\nHorizon 2020 research and innovation
programme under the Marie Skłodowska-Curie grant\r\nagreement (No 101034413, to
K.L.)."
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
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full_name: Lin, Peipeng
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citation:
ama: 'Lin P. Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses. 2026. doi:10.15479/AT-ISTA-22735'
apa: 'Lin, P. (2026). Calibrating the teacher synapse: Mechanisms and functional
significance of presynaptic inhibition at hippocampal mossy fiber synapses.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT-ISTA-22735'
chicago: 'Lin, Peipeng. “Calibrating the Teacher Synapse: Mechanisms and Functional
Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.” Institute
of Science and Technology Austria, 2026. https://doi.org/10.15479/AT-ISTA-22735.'
ieee: 'P. Lin, “Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses,” Institute of Science
and Technology Austria, 2026.'
ista: 'Lin P. 2026. Calibrating the teacher synapse: Mechanisms and functional significance
of presynaptic inhibition at hippocampal mossy fiber synapses. Institute of Science
and Technology Austria.'
mla: 'Lin, Peipeng. Calibrating the Teacher Synapse: Mechanisms and Functional
Significance of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses.
Institute of Science and Technology Austria, 2026, doi:10.15479/AT-ISTA-22735.'
short: 'P. Lin, Calibrating the Teacher Synapse: Mechanisms and Functional Significance
of Presynaptic Inhibition at Hippocampal Mossy Fiber Synapses, Institute of Science
and Technology Austria, 2026.'
corr_author: '1'
das_tickbox: '0'
date_created: 2026-08-18T15:23:41Z
date_published: 2026-08-25T00:00:00Z
date_updated: 2026-09-16T07:39:42Z
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call_identifier: H2020
grant_number: '692692'
name: Biophysics and circuit function of a giant cortical glutamatergic synapse
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grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
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name: Mechanisms of GABA release in hippocampal circuits
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publisher: Institute of Science and Technology Austria
researchdata_availability: upon request
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supervisor:
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full_name: Jonas, Peter M
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apa: Jamrichova, S. (2026). Timing and strength of synaptic transmission at hippocampal
mossy fiber synapses in mice and humans. Institute of Science and Technology
Austria. https://doi.org/10.15479/AT-ISTA-22775
chicago: Jamrichova, Silvia. “Timing and Strength of Synaptic Transmission at Hippocampal
Mossy Fiber Synapses in Mice and Humans.” Institute of Science and Technology
Austria, 2026. https://doi.org/10.15479/AT-ISTA-22775.
ieee: S. Jamrichova, “Timing and strength of synaptic transmission at hippocampal
mossy fiber synapses in mice and humans,” Institute of Science and Technology
Austria, 2026.
ista: Jamrichova S. 2026. Timing and strength of synaptic transmission at hippocampal
mossy fiber synapses in mice and humans. Institute of Science and Technology Austria.
mla: Jamrichova, Silvia. Timing and Strength of Synaptic Transmission at Hippocampal
Mossy Fiber Synapses in Mice and Humans. Institute of Science and Technology
Austria, 2026, doi:10.15479/AT-ISTA-22775.
short: S. Jamrichova, Timing and Strength of Synaptic Transmission at Hippocampal
Mossy Fiber Synapses in Mice and Humans, Institute of Science and Technology Austria,
2026.
corr_author: '1'
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call_identifier: H2020
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name: Biophysics and circuit function of a giant cortical glutamatergic synapse
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grant_number: '101199096'
name: Synaptic mechanisms of engram storage and retrieval in CA3 hippocampal microcircuits
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publication_status: published
publisher: Institute of Science and Technology Austria
researchdata_availability: upon request
status: public
supervisor:
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full_name: Jonas, Peter M
id: 353C1B58-F248-11E8-B48F-1D18A9856A87
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orcid: 0000-0001-5001-4804
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in mice and humans
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...