VIP Interneurons Contribute to Avoidance Behavior by Regulating Information Flow across Hippocampal-Prefrontal Networks

Inhibitory interneurons expressing vasoactive intestinal polypeptide (VIP) are known to disinhibit cortical neurons. However, it is unclear how disinhibition, occurring at the single-cell level, interacts with network-level patterns of activity to shape complex behaviors. To address this, we examined the role of prefrontal VIP interneurons in a widely studied mouse behavior: deciding whether to explore or avoid the open arms of an elevated plus maze. VIP interneuron activity increases in the open arms and disinhibits prefrontal responses to hippocampal inputs, which are known to transmit signals related to open arm avoidance. Indeed, inhibiting VIP interneurons disrupts network-level representations of the open arms and decreases open arm avoidance specifically when hippocampal-prefrontal theta synchrony is strong. Thus, VIP interneurons effectively gate the ability of hippocampal input to generate prefrontal representations, which drive avoidance behavior. This shows how VIP interneurons enable cortical circuits to integrate specific inputs into network-level representations that guide complex behaviors. VIDEO ABSTRACT