A disinhibitory basal forebrain to cortex projection supports sustained attention

Kavli Affiliate: Edward Callaway

| Authors: Shu-Jing Li, Balazs Hangya, Unmukt Gupta, Kyle B. Fischer, James Fitzhugh Sturgill, Edward M. Callaway and Adam Kepe

| Summary:

Sustained attention, as an essential cognitive faculty governing selective sensory processing, exhibits remarkable temporal fluctuations. However, the underlying neural circuits and computational mechanisms driving moment-to-moment attention fluctuations remain elusive. Here we demonstrate that cortex-projecting basal forebrain parvalbumin-expressing inhibitory neurons (BF-PV) mediate sustained attention in mice performing an attention task. BF-PV activity predicts the fluctuations of attentional performance metrics ― reaction time and accuracy ― trial-by-trial, and optogenetic activation of these neurons enhances performance. BF-PV neurons also respond to motivationally salient events, such as predictive cues, rewards, punishments, and surprises, which a computational model explains as representing motivational salience for allocating attention over time. Furthermore, we found that BF-PV neurons produce cortical disinhibition by inhibiting cortical PV+ inhibitory neurons, potentially underpinning the observed attentional gain modulation in the cortex. These findings reveal a disinhibitory BF-to-cortex projection that regulates cortical gain based on motivational salience, thereby promoting sustained attention. HIGHLIGHTS BF-PV activity predicts attentional performance metrics: reaction time and accuracy BF-PV responses reflect the computation of motivational salience-guided attention allocation Optogenetic activation of BF-PV neurons improves attentional performance BF-PV neurons produce cortical disinhibition through topographic projections and mediate gain modulation

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