Cortex-wide activation of VIP-expressing inhibitory neurons by reward and punishment

Canonical neural circuit motifs are assemblies of connected cell types that are repeated across areas. Recent studies identified a cortical circuit motif controlled by VIP interneurons, which preferentially inhibit other interneurons and thereby disinhibit principal neurons. As a previous work showed that auditory cortex VIP interneurons respond not only to sensory stimuli but also to reinforcement feedback, we hypothesized that VIP interneurons may transduce global reinforcement signals for local computation. By using 3D random- access two- photon imaging of VIP neurons across the dorsal cortex while mice performed an auditory discrimination task, we found that most VIP neurons across the cortex were robustly activated by reward and punishment and tended to be activated together. Our results reveal that VIP interneurons have multiple response modes with both local and global contributions. We propose that by signaling reinforcement events, VIP interneurons form a new information channel for orchestrating cortex- wide learning mechanisms.