Functionally identified neuronal assemblies robustly encode stimuli and are structurally delineated by inhibition
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.
Authors
- Anton Arkhipov (ORCID: https://orcid.org/0000-0003-1106-8310)
- Josh Larkin
- Ágnes L. Bodor (ORCID: https://orcid.org/0000-0003-2082-9935)
- R. Clay Reid (ORCID: https://orcid.org/0000-0002-8697-6797)
- Kevin Takasaki (ORCID: https://orcid.org/0009-0000-1531-6022)
- Daniel J. Denman (ORCID: https://orcid.org/0000-0003-1075-1265)
- Jun Zhuang (ORCID: https://orcid.org/0000-0002-6237-3270)
- JoAnn Buchanan (ORCID: https://orcid.org/0000-0002-4212-5560)
- Jérôme Lecoq (ORCID: https://orcid.org/0000-0002-0131-0938)
- Nuno Maçarico da Costa (ORCID: https://orcid.org/0000-0003-2001-4568)
- Joseph W. Aman (ORCID: https://orcid.org/0000-0001-6659-1809)
- Sai Kate
- Reza Abbasi-Asl (ORCID: https://orcid.org/0000-0001-7824-4628)
- Jan Mölter (ORCID: https://orcid.org/0000-0002-5964-6207)
- Emily Joyce (ORCID: https://orcid.org/0000-0001-5794-6321)
- Adam Amster (ORCID: https://orcid.org/0000-0002-5724-7472)
- Trevor Riordan
- David G Wyrick (ORCID: https://orcid.org/0000-0001-8096-5766)
- Jack Waters (ORCID: https://orcid.org/0000-0002-2312-4183)
- Daniel J. Bumbarger (ORCID: https://orcid.org/0000-0001-6224-1633)
- Wenjing Yin (ORCID: https://orcid.org/0000-0002-3307-9160)
- Chase W. King (ORCID: https://orcid.org/0000-0002-0817-1272)
- Saskia de Vries (ORCID: https://orcid.org/0000-0002-3704-3499)
- Ştefan Mihalaş (ORCID: https://orcid.org/0000-0002-2629-7100)
- Gayathri Mahalingam (ORCID: https://orcid.org/0000-0003-3718-5013)
- Daniel Millman (ORCID: https://orcid.org/0000-0002-6255-6085)
- Forrest Collman (ORCID: https://orcid.org/0000-0002-0280-7022)
- Stefan Berteau (ORCID: https://orcid.org/0000-0003-3664-9429)
- Michael A. Buice (ORCID: https://orcid.org/0000-0002-2196-1498)
- Julian Wagner-Carena (ORCID: https://orcid.org/0000-0002-4039-5647)
- David Vumbaco (ORCID: https://orcid.org/0000-0001-8115-3081)
- Derrick Brittain (ORCID: https://orcid.org/0000-0003-3890-2862)
- Daniel Kapner
- Chris Morrison
- Casey M Schneider-Mizell
- Russel Torres
- Marc Takeno
- Shelby Suckow
- Scott Daniel
Institutions
- Georgia Institute of Technology (US)
- Harvard University (US)
- University of California, San Francisco (US)
- Allen Institute (US)
- Technical University of Munich (DE)
Publication Details
- Journal
- Cell Reports
- Published
- 2026-08-28
- DOI
- https://doi.org/10.1016/j.celrep.2026.117900
- Primary Topic
- Neural dynamics and brain function
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- National Institutes of Health