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Peer-reviewedCC BY-NCCell reports

Functionally identified neuronal assemblies robustly encode stimuli and are structurally delineated by inhibition

27 more authors
  1. 1Allen Institute, Seattle, WA, USA
  2. 2Department of Mathematics, School of Computation, Information and Technology, Technical University of Munich, 85748 Garching bei München, Germany

Abstract

SUMMARY: In 1949, Donald Hebb proposed that neuronal assemblies with temporally specific patterns of activity form the building blocks of perception, cognition, and behavior. Finding the structural underpinning of such assemblies has been technically challenging due to a lack of large-scale structure-activity maps. Here, we combine in vivo optical physiology with postmortem electron microscopy (EM) in the same tissue volume. Using higher-order correlations in fluorescence traces, we extract neuronal assemblies. Physiologically, we show that these assemblies respond more reliably to repeated natural movies than size-matched control ensembles and decode such stimuli more accurately. Structurally, we find that over a quarter of the pyramidal neurons do not participate in any assembly and are significantly less integrated into the connectome than those that do. We do not observe a marked increase in the strength of monosynaptic excitatory connections between neurons sharing assembly assignment, but instead find significantly stronger indirect inhibitory connections targeting cells in other assemblies. These results show that assemblies can serve as functional units of perception and suggest they may be structurally delineated by mutual inhibition.

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BibTeX
@article{wagnercarena2026functionally,
  title = {{Functionally identified neuronal assemblies robustly encode stimuli and are structurally delineated by inhibition}},
  author = {Julian Wagner-Carena and Sai Kate and Trevor Riordan and Reza Abbasi-Asl and Joseph Aman and Adam Amster and Anton Arkhipov and Agnes L. Bodor and Derrick Brittain and JoAnn Buchanan and Michael A. Buice and Daniel J. Bumbarger and Forrest Collman and Nuno Maçarico da Costa and Scott Daniel and Daniel J. Denman and Saskia E.J. de Vries and Emily Joyce and Daniel Kapner and Chase W. King and Josh D. Larkin and Jerome Lecoq and Gayathri Mahalingam and Daniel Millman and Jan Mölter and Chris Morrison and R. Clay Reid and Casey M. Schneider-Mizell and Shelby Suckow and Kevin T. Takasaki and Marc Takeno and Russel Torres and David Vumbaco and Jack Waters and David G. Wyrick and Wenjing Yin and Jun Zhuang and Stefan Mihalas and Stefan Berteau},
  journal = {Cell reports},
  year = {2026},
  month = aug,
  doi = {10.1016/j.celrep.2026.117900},
  url = {https://europepmc.org/article/PMC/PMC13722110},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Functionally identified neuronal assemblies robustly encode stimuli and are structurally delineated by inhibition
AU  - Julian Wagner-Carena
AU  - Sai Kate
AU  - Trevor Riordan
AU  - Reza Abbasi-Asl
AU  - Joseph Aman
AU  - Adam Amster
AU  - Anton Arkhipov
AU  - Agnes L. Bodor
AU  - Derrick Brittain
AU  - JoAnn Buchanan
AU  - Michael A. Buice
AU  - Daniel J. Bumbarger
AU  - Forrest Collman
AU  - Nuno Maçarico da Costa
AU  - Scott Daniel
AU  - Daniel J. Denman
AU  - Saskia E.J. de Vries
AU  - Emily Joyce
AU  - Daniel Kapner
AU  - Chase W. King
AU  - Josh D. Larkin
AU  - Jerome Lecoq
AU  - Gayathri Mahalingam
AU  - Daniel Millman
AU  - Jan Mölter
AU  - Chris Morrison
AU  - R. Clay Reid
AU  - Casey M. Schneider-Mizell
AU  - Shelby Suckow
AU  - Kevin T. Takasaki
AU  - Marc Takeno
AU  - Russel Torres
AU  - David Vumbaco
AU  - Jack Waters
AU  - David G. Wyrick
AU  - Wenjing Yin
AU  - Jun Zhuang
AU  - Stefan Mihalas
AU  - Stefan Berteau
PY  - 2026
DA  - 2026/08/27
JO  - Cell reports
DO  - 10.1016/j.celrep.2026.117900
UR  - https://europepmc.org/article/PMC/PMC13722110
AB  - SUMMARY: In 1949, Donald Hebb proposed that neuronal assemblies with temporally specific patterns of activity form the building blocks of perception, cognition, and behavior. Finding the structural underpinning of such assemblies has been technically challenging due to a lack of large-scale structure-activity maps. Here, we combine in vivo optical physiology with postmortem electron microscopy (EM) in the same tissue volume. Using higher-order correlations in fluorescence traces, we extract neuronal assemblies. Physiologically, we show that these assemblies respond more reliably to repeated natural movies than size-matched control ensembles and decode such stimuli more accurately. Structurally, we find that over a quarter of the pyramidal neurons do not participate in any assembly and are significantly less integrated into the connectome than those that do. We do not observe a marked increase in the strength of monosynaptic excitatory connections between neurons sharing assembly assignment, but instead find significantly stronger indirect inhibitory connections targeting cells in other assemblies. These results show that assemblies can serve as functional units of perception and suggest they may be structurally delineated by mutual inhibition.
SN  - 2211-1247
ER  -