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A claustro-cortical loop times state transitions for flexible behavior

Created on 17 Jul 2026

Authors

Olson, R. J., Sonneborn, A., Milton, R., Bartlett, L., Abbas, A.

Abstract

Metastable dynamics, in which neural activity moves between transiently stable patterns, have been proposed to underlie the real-time coordination on which the brain's cognitive and behavioral functions depend. In the cortex, the simplest form of this regime is the alternation between active 'UP' states, in which neurons fire, and silent 'DOWN' states, in which firing is strongly reduced, a bistable architecture that shapes how afferent information is processed. Such metastable dynamics are ubiquitous across cortex, yet how their state transitions are timed and controlled, and how this timing shapes behavior, remain open questions. Here we show, in freely behaving mice performing a cue-guided switching task, that the metastable dynamics of frontal cortex are jointly shaped by its reciprocal loop with the claustrum, a small and widely connected subcortical structure, and that the loop's timing of these state transitions is required for efficient flexible behavior. Claustrum activity led the cortical UP-to-DOWN state transition, delivering to anterior cingulate cortex a low-dimensional drive aligned with the axis along which the cortical state switches. This drive was carried not by a rise in claustral firing but by transient coordination: population synchrony peaked at the transition even as mean rate fell. Silencing ACC-projecting claustrum terminals reduced directed claustro-cortical coupling, biased cortex away from the DOWN state by prolonging UP states and shortening DOWN states, and selectively impaired cue-driven switching while sparing exploratory foraging. These results place flexible behavior under the control of a defined cortico-subcortical loop that times cortical state transitions, offering a circuit-level entry point into the cognitive rigidity of many psychiatric and neurological conditions.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 17 Jul 2026.

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