Selective ablation of VIP interneurons in the rodent prefrontal cortex results in increased impulsivity

It has been well-established that novelty-seeking and impulsivity are significant risk factors for the development of psychological disorders, including substance use disorder and behavioral addictions. While dysfunction in the prefrontal cortex is at the crux of these disorders, little is known at the cellular level about how alterations in neuron activity can drive changes in impulsivity and novelty seeking. We harnessed a cre-dependent caspase-3 ablation in both male and female mice to selectively ablate vasoactive intestinal peptide (VIP)-expressing interneurons in the prefrontal cortex to better explore how this microcircuit functions during specific behavioral tasks. Caspase-ablated animals had no changes in anxiety-like behaviors or hedonic food intake but had a specific increase in impulsive responding during longer trials in the three-choice serial reaction time test. Together, these data suggest a circuit-level mechanism in which VIP interneurons function as a gate to selectively respond during periods of high expectation.