State-Dependent Regulation of Cortical Processing Speed via Gain Modulation.

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 corticocortical 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 counterintuitive 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.SIGNIFICANCE STATEMENT To thrive in dynamic environments, animals adapt their behavior to changing circumstances and different internal states. Examples of behavioral flexibility include faster responses to sensory stimuli when attentive and slower responses when distracted. Previous work suggested that contextual modulations may be implemented via top-down inputs to sensory cortex coming from higher brain areas or neuromodulatory pathways. Here, we introduce a theory explaining how the speed at which sensory cortex processes incoming information is adjusted by changes in these top-down projections, which control the timescale of neural activity. We tested our model predictions in freely running mice, revealing that locomotion accelerates visual processing. Our theory is applicable to internal modulation as well as optogenetic and pharmacological manipulations and links circuit connectivity, dynamics, and information processing.