---
OA_place: repository
_id: '18688'
abstract:
- lang: eng
text: The human brain has remarkable computational power. It generates sophisticated
behavioral sequences, stores engrams over an individual’s lifetime, and produces
higher cognitive functions up to the level of consciousness. However, so little
of our neuroscience knowledge covers the human brain, and it remains unknown whether
this organ is truly unique, or is a scaled version of the extensively studied
rodent brain. To address this fundamental question, we determined the cellular,
synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using
multicellular patch clamp-recording. This circuit is the largest autoassociative
network in the brain, and plays a key role in memory and higher-order computations
such as pattern separation and pattern completion. We demonstrate that human hippocampal
CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks.
Connectivity sparsifies from rodents to humans, providing a circuit architecture
that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses
showed both distinct species-specific and circuit-dependent properties, with high
reliability, unique amplitude precision, and long integration times. We also identify
differential scaling rules between hippocampal pathways from rodents to humans,
with a moderate increase in the convergence of CA3 inputs per cell, but a marked
increase in human mossy fiber innervation. Anatomically guided full-scale modeling
suggests that the human brain’s sparse connectivity, expanded neuronal number,
and reliable synaptic signaling combine to enhance the associative memory storage
capacity of CA3. Together, our results reveal unique rules of connectivity and
synaptic signaling in the human hippocampus, demonstrating the absolute necessity
of human brain research and beginning to unravel the remarkable performance of
our autoassociative memory circuits.
acknowledged_ssus:
- _id: Bio
- _id: LifeSc
- _id: M-Shop
- _id: PreCl
- _id: ScienComp
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, and Eleftheria
Kralli-Beller for manuscript editing. This research was supported by the Scientific
Services Units (SSUs) of ISTA, and we are particularly grateful for assistance from
Christoph Sommer and the Imaging and Optics Facility, Preclinical Facility, Life
Science Facility, Miba Machine Shop, and Scientific Computing. We also acknowledge
the excellent support of the Medical University of Vienna Department of Neurosurgery
staff, Romana Hoeftberger and the Division of Neuropathology and Neurochemistry,
and Gregor Kasprian and the Division of Neuroradiology and Musculoskeletal Radiology.
The project received funding from the European Research Council (ERC) under the
European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie
Actions Individual Fellowship no. 101026635 to J.F.W.), the Austrian Science Fund
(FWF; grant PAT 4178023 to P.J.; grant DK W1232 to M.R.T. and J.G.D.) and the Austrian
Academy of Sciences (DOC fellowship 26137 to M.R.T.).
article_processing_charge: No
author:
- first_name: Jake F.
full_name: Watson, Jake F.
last_name: Watson
- first_name: Victor
full_name: Vargas-Barroso, Victor
last_name: Vargas-Barroso
- first_name: Rebecca J.
full_name: Morse-Mora, Rebecca J.
last_name: Morse-Mora
- first_name: Andrea
full_name: Navas-Olive, Andrea
last_name: Navas-Olive
- first_name: Mojtaba
full_name: Tavakoli, Mojtaba
id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87
last_name: Tavakoli
orcid: 0000-0002-7667-6854
- first_name: Johann G
full_name: Danzl, Johann G
id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87
last_name: Danzl
orcid: 0000-0001-8559-3973
- first_name: Matthias
full_name: Tomschik, Matthias
last_name: Tomschik
- first_name: Karl
full_name: Rössler, Karl
last_name: Rössler
- 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: Watson JF, Vargas-Barroso V, Morse-Mora RJ, et al. Human hippocampal CA3 uses
specific functional connectivity rules for efficient associative memory. bioRxiv.
doi:10.1101/2024.05.02.592169
apa: Watson, J. F., Vargas-Barroso, V., Morse-Mora, R. J., Navas-Olive, A., Tavakoli,
M., Danzl, J. G., … Jonas, P. M. (n.d.). Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv. https://doi.org/10.1101/2024.05.02.592169
chicago: Watson, Jake F., Victor Vargas-Barroso, Rebecca J. Morse-Mora, Andrea Navas-Olive,
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.” BioRxiv, n.d. https://doi.org/10.1101/2024.05.02.592169.
ieee: J. F. Watson et al., “Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory,” bioRxiv. .
ista: Watson JF, Vargas-Barroso V, Morse-Mora RJ, Navas-Olive A, Tavakoli M, Danzl
JG, Tomschik M, Rössler K, Jonas PM. Human hippocampal CA3 uses specific functional
connectivity rules for efficient associative memory. bioRxiv, 10.1101/2024.05.02.592169.
mla: Watson, Jake F., et al. “Human Hippocampal CA3 Uses Specific Functional Connectivity
Rules for Efficient Associative Memory.” BioRxiv, doi:10.1101/2024.05.02.592169.
short: J.F. Watson, V. Vargas-Barroso, R.J. Morse-Mora, A. Navas-Olive, M. Tavakoli,
J.G. Danzl, M. Tomschik, K. Rössler, P.M. Jonas, BioRxiv (n.d.).
corr_author: '1'
date_created: 2024-12-19T11:35:08Z
date_published: 2024-05-02T00:00:00Z
date_updated: 2026-07-28T08:33:51Z
day: '02'
department:
- _id: JoDa
- _id: PeJo
doi: 10.1101/2024.05.02.592169
ec_funded: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1101/2024.05.02.592169
month: '05'
oa: 1
oa_version: Preprint
project:
- _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9
call_identifier: H2020
grant_number: '101026635'
name: Synaptic computations of the hippocampal CA3 circuitry
- _id: 26AA4EF2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: W1232-B24
name: Molecular Drug Targets
- _id: 6285a163-2b32-11ec-9570-8e204ca2dba5
grant_number: '26137'
name: Studying Organelle Structure and Function at Nanoscale Resolution with Expansion
Microscopy
publication: bioRxiv
publication_status: draft
related_material:
record:
- id: '18879'
relation: later_version
status: public
- id: '18681'
relation: dissertation_contains
status: public
status: public
title: Human hippocampal CA3 uses specific functional connectivity rules for efficient
associative memory
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2024'
...