Julian Wagner-Carena, Sai Kate, Trevor Riordan, Reza Abbasi-Asl, Joseph Aman, Adam Amster, Anton Arkhipov, Agnes L Bodor, Derrick Brittain, JoAnn Buchanan, Michael A Buice, Daniel J Bumbarger, Forrest Collman, Nuno Maçarico da Costa, Scott Daniel, Daniel J Denman, Saskia E J de Vries, Emily Joyce, Daniel Kapner, Chase W King, Josh D Larkin, Jerome Lecoq, Gayathri Mahalingam, Daniel Millman, Jan Mölter, Chris Morrison, R Clay Reid, Casey M Schneider-Mizell, Shelby Suckow, Kevin T Takasaki, Marc Takeno, Russel Torres, David Vumbaco, Jack Waters, David G Wyrick, Wenjing Yin, Jun Zhuang, Stefan Mihalas, Stefan Berteau
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.