Novel stimuli evoke excess activity in the mouse primary visual cortex

Significance Rapid detection and processing of stimulus novelty are key elements of adaptive behavior. Predictive coding theories postulate that novel stimuli should be encoded differently from familiar stimuli. Here, we show that the majority of neurons in layer 2/3 of the mouse primary visual cortex exhibit a significant excess response to novel visual stimuli. The distinction between novel and familiar images developed rapidly, requiring only a few repeated presentations. We show that this phenomenon can be described by a model of cascading adaptation. This ubiquitous mechanism makes it likely that similar computations could be carried out in many brain areas.