A class of interneurons expressing vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of the neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, the study examined the functional role of VIP interneurons in awake mice and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. The researchers identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells. During an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in the auditory cortex, and in turn, VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell-type and microcircuit underlying disinhibitory control in the cortex and demonstrate that it is activated under specific behavioral conditions. VIP interneurons function within a highly interconnected network, serving as pre-synaptic drivers of ('impact') and post-synaptic responders to ('recruitment') other neurons. The study shows that VIP neurons mediate disinhibitory control, and a behaviorally relevant condition, reinforcement feedback, uniformly activates VIP neurons. The homogeneous behavioral recruitment of VIPs suggests that the synchronous ChR2-mediated activation to probe their circuit function was physiologically plausible. VIP interneurons are ideally positioned to serve as a substrate for long-range inputs to increase the gain of local cortical processing. The study also demonstrates that VIP interneurons provide a powerful circuit mechanism that enables long-range cortical signals or subcortical neuromodulation to efficiently modulate specific pyramidal neuron ensembles. The findings highlight the role of VIP interneurons in cortical microcircuits and their potential for cortical learning mechanisms.A class of interneurons expressing vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of the neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, the study examined the functional role of VIP interneurons in awake mice and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. The researchers identified a basic disinhibitory circuit module in which activation of VIP interneurons transiently suppresses primarily somatostatin- and a fraction of parvalbumin-expressing inhibitory interneurons that specialize in the control of the input and output of principal cells. During an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in the auditory cortex, and in turn, VIP recruitment increased the gain of a functional subpopulation of principal neurons. These results reveal a specific cell-type and microcircuit underlying disinhibitory control in the cortex and demonstrate that it is activated under specific behavioral conditions. VIP interneurons function within a highly interconnected network, serving as pre-synaptic drivers of ('impact') and post-synaptic responders to ('recruitment') other neurons. The study shows that VIP neurons mediate disinhibitory control, and a behaviorally relevant condition, reinforcement feedback, uniformly activates VIP neurons. The homogeneous behavioral recruitment of VIPs suggests that the synchronous ChR2-mediated activation to probe their circuit function was physiologically plausible. VIP interneurons are ideally positioned to serve as a substrate for long-range inputs to increase the gain of local cortical processing. The study also demonstrates that VIP interneurons provide a powerful circuit mechanism that enables long-range cortical signals or subcortical neuromodulation to efficiently modulate specific pyramidal neuron ensembles. The findings highlight the role of VIP interneurons in cortical microcircuits and their potential for cortical learning mechanisms.