The claustrum contributes to working memory maintenance in mice

Abstract Working memory (WM) enables the temporary maintenance and manipulation of sensory information to guide behavior, yet the neural circuits supporting this process remain incompletely defined. The claustrum is a highly interconnected brain structure positioned to integrate distributed cortical activity, but its contribution to WM has remained unclear. Here, we combined microendoscopic calcium imaging, chemogenetic and optogenetic manipulations in mice performing sensory-guided WM tasks to examine the role of the claustrum in WM. Claustrum neurons exhibited cue-evoked activity that persisted across delay periods and evolved dynamically over time, with population states retaining information about cue identity on single trials. Reducing claustrum excitability during encoding, delay maintenance, or target comparison similarly impaired WM performance across sensory modalities, without affecting sensory processing, motor output, arousal or inhibitory control. Together, these findings reveal an important causal contribution of the claustrum to WM maintenance.