Neurons embedded in loop‐like motifs act as central hubs for brain‐wide integration

Efficient cooperation between brain areas requires a dynamic balance between thesegregation of region-specific functional roles and information broadcasting. Imaging studies ofbrain-wide co-ordination cannot reach the single-cell assembly level analysis. In this study, weexplored co-ordinative relationships between single neurons across 71 mouse brain regions using theconcept of cell assembly as an investigative tool. Cell assemblies can be considered the fundamentalbrain processing units, and identifying their aggregate structure can provide a high-resolution viewof inter-regional co-ordinative relationships. We first examined pairwise co-ordination betweenareas, and then we investigated higher-order forms of inter-regional connectivity, searching fortriplets of neurons. We mainly focused on one functionally relevant motif: the loop-like triplet,modelling a reentrant flow of information, which we hypothesised could represent a core mechanismfor the integration of information. We found that this reentrant mode of communication was oftenasymmetrical between areas and largely unrelated to neuron pair co-ordination. We found that hubneurons, which have a higher-than-average number of co-ordinative relationships with externalregions, are consistently and significantly embedded in loop-like assemblies. These findings suggestthat this peculiar motif represents a core architectural feature supporting brain-wide integration.