Sensory cortices must flexibly adapt their operations to internal states and external requirements. Modulation of specific inhibitory interneurons may provide a network-level mechanism for adjustments on behaviourally relevant timescales. Understanding of the computational roles of such modulation has mostly been restricted to phasic optogenetic activation and short, transient stimuli. Here, we aimed to extend the understanding of modulation of cortical inhibition by using sustained, network-wide optogenetic activation of parvalbumin-positive interneurons in core auditory cortex to study modulation of responses to transient, sustained, and naturalistic stimuli. We found highly conserved spectral and temporal tuning, despite profoundly reduced overall network activity. This reduction was predominantly divisive, and consistent across simple, complex, and naturalistic stimuli. A recurrent network model with power-law input-output functions replicated our results. We conclude that modulation of parvalbumin-positive interneurons on timescales typical of more sustained neuromodulation may provide a means for robust divisive gain control conserving stimulus representations.

Sustained Activation of PV+ Interneurons in Core Auditory Cortex Enables Robust Divisive Gain Control for Complex and Naturalistic Stimuli