Dorsal prefrontal cortex drives perseverative behavior in mice

Perseveration – repeating one choice when others would generate larger rewards – is a common behavior, but neither its purpose nor neuronal mechanisms are understood. Here we demonstrate a neural correlate and causal role of dorsal prefrontal cortex (area MOs) in perseveration in mice performing a dynamic reward learning task. An auditory go cue signaled mice to turn a wheel either left or right, with the reward probability of each action switching in blocks. Mice perseverated, gaining suboptimal reward, but were faster when making repeated choices. Neuropixels recordings found neurons whose activity correlated with perseveration and predicted rapid reaction times, almost exclusively in MOs. Optogenetically inhibiting MOs reduced perseveration and slowed reaction times. In contrast, inactivating medial prefrontal cortex at choice time did not have any effect but impaired learning if delivered after reward delivery. In this task, therefore, MOs encodes a perseverative decision variable, and is necessary for mediating the effect of this decision variable on choice and reaction time.