Cortical inhibitory interneurons expressing vasoactive intestinal polypeptide (VIP) are shown to specialize in suppressing the activity of other inhibitory interneurons and are activated by reinforcement signals, thus increasing the activity of excitatory neurons by releasing them from inhibition; these results reveal a cell-type-specific microcircuit that tunes cortical activity under certain behavioural conditions. Disinhibition is a potentially powerful mechanism for controlling the activity and computation in neural circuits. Relatively little is known about neurons specializing in disinhibition and their specific function. Now Adam Kepecs and colleagues report that a cortical interneuron type defined by vasoactive intestinal polypeptide (VIP) expression inhibits the activity of other inhibitory interneurons, thereby adding an additional level of control over excitatory neurons. They further find that VIP interneurons are activated by rewards and punishments when rats perform a reinforcement learning task. These results reveal a cell-type-specific microcircuit that tunes cortical activity under certain behavioural conditions. In the mammalian cerebral cortex the diversity of interneuronal subtypes underlies a division of labour subserving distinct modes of inhibitory control1,2,3,4,5,6,7. A unique mode of inhibitory control may be provided by inhibitory neurons that specifically suppress the firing of other inhibitory neurons. Such disinhibition could lead to the selective amplification of local processing and serve the important computational functions of gating and gain modulation8,9. Although several interneuron populations are known to target other interneurons to varying degrees10,11,12,13,14,15, little is known about interneurons specializing in disinhibition and their in vivo function. Here we show that a class of interneurons that express vasoactive intestinal polypeptide (VIP) mediates disinhibitory control in multiple areas of neocortex and is recruited by reinforcement signals. By combining optogenetic activation with single-cell recordings, we examined the functional role of VIP interneurons in awake mice, and investigated the underlying circuit mechanisms in vitro in auditory and medial prefrontal cortices. We 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, respectively3,6,16,17. During the performance of an auditory discrimination task, reinforcement signals (reward and punishment) strongly and uniformly activated VIP neurons in 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 cortex and demonstrate that it is activated under specific behavioural conditions.

Cortical interneurons that specialize in disinhibitory control