RT Journal Article SR Electronic T1 State-dependent regulation of cortical processing speed via gain modulation JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.04.07.030700 DO 10.1101/2020.04.07.030700 A1 David Wyrick A1 Luca Mazzucato YR 2021 UL http://biorxiv.org/content/early/2021/01/25/2020.04.07.030700.abstract AB To thrive in dynamic environments, animals must be capable of rapidly and flexibly adapting behavioral responses to a changing context and internal state. Examples of behavioral flexibility include faster stimulus responses when attentive and slower responses when distracted. Contextual or state-dependent modulations may occur early in the cortical hierarchy and may be implemented via top-down projections from cortico-cortical or neuromodulatory pathways. However, the computational mechanisms mediating the effects of such projections are not known. Here, we introduce a theoretical framework to classify the effects of cell-type specific top-down perturbations on the information processing speed of cortical circuits. Our theory demonstrates that perturbation effects on stimulus processing can be predicted by intrinsic gain modulation, which controls the timescale of the circuit dynamics. Our theory leads to counter-intuitive effects such as improved performance with increased input variance. We tested the model predictions using large-scale electrophysiological recordings from the visual hierarchy in freely running mice, where we found that a decrease in single-cell intrinsic gain during locomotion led to an acceleration of visual processing. Our results establish a novel theory of cell-type specific perturbations, applicable to top-down modulation as well as optogenetic and pharmacological manipulations. Our theory links connectivity, dynamics, and information processing via gain modulation.Competing Interest StatementThe authors have declared no competing interest.