Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory
Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.
Download
Journal Article
| Published
| English
Scopus indexed
Author
Watson, JakeISTA 
;
Vargas Barroso, Victor MISTA;
Morse, RebeccaISTA;
Navas Olivé, Andrea CISTA ;
R. Tavakoli, MojtabaISTA ;
Danzl, Johann GISTA ;
Tomschik, Matthias;
Rössler, Karl;
Jonas, Peter MISTA
;
Vargas Barroso, Victor MISTA;
Morse, RebeccaISTA;
Navas Olivé, Andrea CISTA ;
R. Tavakoli, MojtabaISTA ;
Danzl, Johann GISTA ;
Tomschik, Matthias;
Rössler, Karl;
Jonas, Peter MISTA Corresponding author has ISTA affiliation
Department
Grant
Abstract
Our brain has remarkable computational power, generating sophisticated behaviors, storing memories over an individual’s lifetime, and producing higher cognitive functions. However, little of our neuroscience knowledge covers the human brain. Is this organ truly unique, or is it a scaled version of the extensively studied rodent brain? Combining multicellular patch-clamp recording with expansion-based superresolution microscopy and full-scale modeling, we determined the cellular and microcircuit properties of the human hippocampal CA3 region, a fundamental circuit for memory storage. In contrast to neocortical networks, human hippocampal CA3 displayed sparse connectivity, providing a circuit architecture that maximizes associational power. Human synapses showed unique reliability, high precision, and long integration times, exhibiting both species- and circuit-specific properties. Together with expanded neuronal numbers, these circuit characteristics greatly enhanced the memory storage capacity of CA3. Our results reveal distinct microcircuit properties of the human hippocampus and begin to unravel the inner workings of our most complex organ.
Publishing Year
Date Published
2025-01-23
Journal Title
Cell
Publisher
Elsevier
Acknowledgement
We thank Florian Marr for excellent technical assistance, Christina Altmutter and Julia Flor for technical support, Alois Schlögl for programming, Todor Asenov for development of the transportation box for human brain tissue, Tim Vogels for guidance on simulations, Marcus Huber for mathematical advice, Walter Kaufmann for assistance with handling frozen tissue, and Eleftheria Kralli-Beller for manuscript editing. This research was supported by the Scientific Services Units (SSUs) of ISTA, and we are grateful for assistance from Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Lab Support Facility, Miba Machine Shop, and Scientific Computing. We are particularly grateful to the patient donors for their support of this project and also acknowledge the excellent support of the Medical University of Vienna Department of Neurosurgery staff; Romana Hoeftberger and the Division of Neuropathology and Neurochemistry; Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology; and Christoph Baumgartner, Martha Feucht, and Ekaterina Pataraia for their clinical care of the patients included in this study. We thank Laura Jonkman, the NABCA biobank, and postmortem brain sample donors for their support of this research. The project received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (advanced grant no. 692692 to P.J. and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund (FWF; grant PAT 4178023 to P.J. and grant DK W1232 to M.R.T. and J.G.D.), the Austrian Academy of Sciences (DOC fellowship 26137 to M.R.T.), and a NOMIS-ISTA fellowship (to A.N.-O.).
Acknowledged SSUs
Volume
188
Issue
2
Page
501-514.e18
ISSN
eISSN
IST-REx-ID
Cite this
Watson J, Vargas Barroso VM, Morse R, et al. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. 2025;188(2):501-514.e18. doi:10.1016/j.cell.2024.11.022
Watson, J., Vargas Barroso, V. M., Morse, R., Navas Olivé, A. C., Tavakoli, M., Danzl, J. G., … Jonas, P. M. (2025). Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. Elsevier. https://doi.org/10.1016/j.cell.2024.11.022
Watson, Jake, Victor M Vargas Barroso, Rebecca Morse, Andrea C Navas Olivé, Mojtaba Tavakoli, Johann G Danzl, Matthias Tomschik, Karl Rössler, and Peter M Jonas. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” Cell. Elsevier, 2025. https://doi.org/10.1016/j.cell.2024.11.022.
J. Watson et al., “Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory,” Cell, vol. 188, no. 2. Elsevier, p. 501–514.e18, 2025.
Watson J, Vargas Barroso VM, Morse R, Navas Olivé AC, Tavakoli M, Danzl JG, Tomschik M, Rössler K, Jonas PM. 2025. Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory. Cell. 188(2), 501–514.e18.
Watson, Jake, et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity Rules for Efficient Associative Memory.” Cell, vol. 188, no. 2, Elsevier, 2025, p. 501–514.e18, doi:10.1016/j.cell.2024.11.022.
All files available under the following license(s):
Creative Commons Attribution 4.0 International Public License (CC-BY 4.0):
Main File(s)
File Name
2025_Cell_Watson.pdf
14.08 MB
Access Level
Open Access
Date Uploaded
2025-01-27
MD5 Checksum
d5a818edc32d249cdf75e1bb5b70a4b7
Material in ISTA:
Earlier Version
Google Scholar