The claustrum is critical for maintaining working memory information

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Abstract

Working memory (WM) enables the mammalian brain to temporarily store and manipulate information, supporting cognitive tasks and communication processes 1,2 . Rather than depending on a single specialized area, WM is thought to operate through a distributed network spanning cortical and subcortical regions 3–5 . A dedicated WM storage area would likely require broad reciprocal connections with various cortical regions to accommodate the diverse range of information WM retains. The claustrum (CLA), with its extensive bidirectional connections to the neocortex 6–9 , presents a compelling candidate for such a role. Here, we examined the involvement of the CLA in WM processes by recording CLA neuronal activity in mice engaged in olfactory and tactospatial delayed non-match-to-sample WM tasks. We identified cue- selective and delay-specific neurons in the CLA that maintained activity for tens of seconds after the stimulus presentation ended. Additionally, population activity in the CLA allowed for decoding of cue identity post-stimulus, although this signal gradually declined over time, aligning with animal behavior. Remarkably, both chemo- and optogenetic inhibition of CLA neurons severely impaired WM performance across multiple types of stored information, highlighting the CLA’s critical role during both cue encoding, delay periods, and target comparison phases. These findings challenge the view that no single brain area is essential for WM storage and support a role for the CLA as an essential WM storage hub.

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