The claustrum is critical for maintaining working memory information

Working memory (WM) is an essential cognitive function allowing the brain to temporarily hold and manipulate information. Rather than residing in a single store, information is believed to be maintained in a distributed network spanning cortical and subcortical regions. Here, we recorded glutamatergic projection neurons of the claustrum, a nucleus reciprocally connected to all cortical regions, in mice engaged in various delayed non-match to sample WM tasks. Claustrum neurons exhibited cue-selective and delay-specific activity, persisting for tens of seconds after stimulus presentation. Population activity allowed decoding of cue identity post-stimulus, though this signal gradually declined, mirroring behavior. Chemo- and optogenetic inhibition of claustrum neurons severely impaired WM performance across tasks, underscoring the claustrum's role during cue encoding, delay maintenance, and target comparison. These findings challenge the notion that no single brain region is indispensable for WM storage and highlight the claustrum as a pivotal hub for the WM engram.