This article explores the role of VIP-expressing interneurons in the mammalian cerebral cortex, focusing on their function in disinhibitory control. The study identifies a class of interneurons that express vasoactive intestinal polypeptide (VIP) and mediate disinhibitory control in multiple areas of the neocortex. These neurons are recruited by reinforcement signals and play a critical role in modulating the activity of other inhibitory neurons, thereby enhancing the gain of principal neurons. The research combines optogenetic activation with single-cell recordings in awake mice and in vitro experiments in auditory and medial prefrontal cortices to investigate the functional role of VIP interneurons. The study reveals a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons. During an auditory discrimination task, reinforcement signals (reward and punishment) strongly activate VIP neurons in the auditory cortex, which in turn increase the gain of a functional subpopulation of principal neurons. These findings demonstrate that VIP interneurons provide a specific cell-type and microcircuit for disinhibitory control in the cortex, which is activated under specific behavioral conditions. The research also shows that VIP interneurons target other interneurons, specifically somatostatin- and parvalbumin-expressing neurons, and that their activation leads to the release of some pyramidal neurons from inhibitory control. The study further demonstrates that VIP interneurons are involved in shaping auditory receptive fields and modulating auditory frequency tuning. The results highlight the importance of VIP interneurons in cortical processing and their potential role in learning and memory. The study provides a detailed understanding of the circuit mechanisms underlying disinhibitory control in the cortex and its functional significance in behavior.This article explores the role of VIP-expressing interneurons in the mammalian cerebral cortex, focusing on their function in disinhibitory control. The study identifies a class of interneurons that express vasoactive intestinal polypeptide (VIP) and mediate disinhibitory control in multiple areas of the neocortex. These neurons are recruited by reinforcement signals and play a critical role in modulating the activity of other inhibitory neurons, thereby enhancing the gain of principal neurons. The research combines optogenetic activation with single-cell recordings in awake mice and in vitro experiments in auditory and medial prefrontal cortices to investigate the functional role of VIP interneurons. The study reveals a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons. During an auditory discrimination task, reinforcement signals (reward and punishment) strongly activate VIP neurons in the auditory cortex, which in turn increase the gain of a functional subpopulation of principal neurons. These findings demonstrate that VIP interneurons provide a specific cell-type and microcircuit for disinhibitory control in the cortex, which is activated under specific behavioral conditions. The research also shows that VIP interneurons target other interneurons, specifically somatostatin- and parvalbumin-expressing neurons, and that their activation leads to the release of some pyramidal neurons from inhibitory control. The study further demonstrates that VIP interneurons are involved in shaping auditory receptive fields and modulating auditory frequency tuning. The results highlight the importance of VIP interneurons in cortical processing and their potential role in learning and memory. The study provides a detailed understanding of the circuit mechanisms underlying disinhibitory control in the cortex and its functional significance in behavior.