The detection of novel stimuli is critical to learn and survive in a dynamic environment. Though novel stimuli powerfully affect brain activity, their impact on specific cell types and circuits is not well understood. Disinhibition is one candidate mechanism for novelty-induced enhancements in activity. Here we characterize the impact of stimulus novelty on disinhibitory circuit components using longitudinal 2-photon calcium imaging of Vip, Sst, and excitatory populations in the mouse visual cortex. Mice learn a behavioral task with stimuli that become highly familiar, then are tested on both familiar and novel stimuli. Mice consistently perform the task with novel stimuli, yet responses to stimulus presentations and stimulus omissions are dramatically altered. Further, we find that novelty modifies coding of visual as well as behavioral and task information. At the population level, the direction of these changes is consistent with engagement of the Vip-Sst disinhibitory circuit. At the single cell level, we identify separate clusters of Vip, Sst, and excitatory cells with unique patterns of novelty-induced coding changes. This study and the accompanying open-access dataset reveals the impact of novelty on sensory and behavioral representations in visual cortical circuits and establishes novelty as a key driver of cellular functional diversity.

In complex environments, animals can adopt diverse strategies to find rewards. How distinct strategies differentially engage brain circuits is not well understood. Here we investigate this question, focusing on the cortical Vip-Sst disinhibitory circuit. We characterize the behavioral strategies used by mice during a visual change detection task. Using a dynamic logistic regression model we find individual mice use mixtures of a visual comparison strategy and a statistical timing strategy. Separately, mice also have periods of task engagement and disengagement. Two-photon calcium imaging shows large strategy dependent differences in neural activity in excitatory, Sst inhibitory, and Vip inhibitory cells in response to both image changes and image omissions. In contrast, task engagement has limited effects on neural population activity. We find the diversity of neural correlates of strategy can be understood parsimoniously as increased activation of the Vip-Sst disinhibitory circuit during the visual comparison strategy which facilitates task appropriate responses.