Li, Shu-Jing, Hangya, Balazs, Gupta, Unmukt, Singh, Harjot, Fischer, Kyle B, Sturgill, James Fitzhugh, Callaway, Edward M, Kepecs, Adam (June 2026) A disinhibitory basal forebrain-to-cortex projection supports sustained attention. Cell, 189 (13). 4140-4158.e9. ISSN 0092-8674
Abstract
The ability to maintain focus wavers over time, impacting performance, yet the neural circuits governing fluctuations in sustained attention remain unclear. The basal forebrain is integral to attention by modulating cortical activity, but recent evidence challenges the role of its signature cholinergic neurons in sustaining attention. Here, we demonstrate that another cortex-projecting basal forebrain cell type, parvalbumin-expressing (BF-PV) inhibitory neurons, mediates sustained attention. In mice performing an attention-demanding task, BF-PV activity predicts trial-by-trial fluctuations in attentional performance metrics-reaction time and accuracy. Bidirectional optogenetic manipulations confirm causality: activation enhances, and inhibition impairs, attention. BF-PV neurons also respond to motivationally salient events-predictive cues, outcomes, and surprises-regardless of valence. A computational model bridges these observations and demonstrates how this signal guides attention allocation. Mechanistically, BF-PV neurons target cortical PV+ interneurons, producing disinhibitory cortical amplification to improve detection sensitivity. These findings reveal a disinhibitory BF-to-cortex projection that regulates cortical gain based on motivational salience, thereby promoting sustained attention.
| Item Type: | Paper |
|---|---|
| Subjects: | organs, tissues, organelles, cell types and functions > tissues types and functions > forebrain organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > tissues types and functions |
| CSHL Authors: | |
| Communities: | CSHL labs > Egeblad lab CSHL labs > Kepecs lab CSHL Post Doctoral Fellows |
| SWORD Depositor: | CSHL Elements |
| Depositing User: | CSHL Elements |
| Date: | 25 June 2026 |
| Date Deposited: | 21 Sep 2026 14:06 |
| Last Modified: | 21 Sep 2026 14:06 |
| PMCID: | PMC13406564 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/42322 |
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