Cortical Control of Spatial Resolution by VIP+ Interneurons.

Neuronal tuning, defined by the degree of selectivity to a specific stimulus, is a hallmark of cortical computation. Understanding the role of GABAergic interneurons in shaping cortical tuning is now possible with the ability to manipulate interneuron classes selectively. Here, we show that interneurons expressing vasoactive intestinal polypeptide (VIP+) regulate the spatial frequency (SF) tuning of pyramidal neurons in mouse visual cortex. Using two-photon calcium imaging and optogenetic manipulations of VIP+ cell activity, we found that activating VIP+ cells elicited a stronger network response to stimuli of higher SFs, whereas suppressing VIP+ cells resulted in a network response shift toward lower SFs. These results establish that cortical inhibition modulates the spatial resolution of visual processing and add further evidence demonstrating that feature selectivity depends, not only on the feedforward excitatory projections into the cortex, but also on dynamic intracortical modulations by specific forms of inhibition. SIGNIFICANCE STATEMENT: We demonstrate that interneurons expressing vasoactive intestinal polypeptide (VIP+) play a causal role in regulating the spatial frequency (SF) tuning of neurons in mouse visual cortex. We show that optogenetic activation of VIP+ cells results in a shift in network preference toward higher SFs, whereas suppressing them shifts the network toward lower SFs. Several studies have shown that VIP+ cells are sensitive to neuromodulation and increase their firing during locomotion, whisking, and pupil dilation and are involved in spatially specific top-down modulation, reminiscent of the effects of top-down attention, and also that attention enhances spatial resolution. Our findings provide a bridge between these studies by establishing the inhibitory circuitry that regulates these fundamental modulations of SF in the cortex.