Opening Holes in the Blanket of Inhibition: Localized Lateral Disinhibition by VIP Interneurons.

Inhibitory interneurons in the neocortex often connect in a promiscuous and extensive fashion, extending a "blanket of inhibition" on the circuit. This raises the problem of how can excitatory activity propagate in the midst of this widespread inhibition. One solution to this problem could be the vasoactive intestinal peptide (VIP) interneurons, which disinhibit other interneurons. To explore how VIP interneurons affect the local circuits, we use two-photon optogenetics to activate them individually in mouse visual cortex in vivo while measuring their output with two-photon calcium imaging. We find that VIP interneurons have narrow axons and inhibit nearby somatostatin interneurons, which themselves inhibit pyramidal cells. Moreover, via this lateral disinhibition, VIP cells in vivo make local and transient "holes" in the inhibitory blanket extended by SOM cells. VIP interneurons, themselves regulated by neuromodulators, may therefore enable selective patterns of activity to propagate through the cortex, by generating a "spotlight of attention". SIGNIFICANCE STATEMENT: Most inhibitory interneurons have axons restricted to a nearby area and target excitatory neighbors indiscriminately, raising the issue of how neuronal activity can propagate through cortical circuits. Vasoactive intestinal peptide-expressing interneurons (VIPs) disinhibit cortical pyramidal cells through inhibition of other inhibitory interneurons, and they have very focused, "narrow" axons. By optogenetically activating single VIPs in live mice while recording the activity of nearby neurons, we find that VIPs break open a hole in blanket inhibition with an effective range of ∼120 μm in lateral cortical space where excitatory activity can propagate.