A prefrontal cortex–brainstem neuronal projection that controls response to behavioural challenge

High-speed tracking of effortful responses and neuronal activity in rats during a forced swim test identifies medial prefrontal cortex (mPFC) neurons that respond during escape-related swimming but not normal locomotion, and optogenetics shows that mPFC neurons projecting to the brainstem dorsal raphe nucleus, which is implicated in depression, modulate this behavioural response to challenge The neural circuitry of choice Disruption of the prefrontal cortex (PFC) area in the human brain can lead either to impulsive behaviour or to a lack of motivation. This study explores the role of particular populations of PFC neurons in mice during a challenging behavioural situation — the forced swim test. The authors identify neurons that respond during forced swimming, but not during normal locomotion. Using optogenetic manipulation, they show that only the specific population of PFC neurons projecting to the brainstem dorsal raphe nucleus, a region implicated in depression, induces changes in behaviour during forced swimming. These results throw light on the neural circuitry underlying normal and pathological patterns of action selection and motivation in behaviour. The prefrontal cortex (PFC) is thought to participate in high-level control of the generation of behaviours (including the decision to execute actions 1 ); indeed, imaging and lesion studies in human beings have revealed that PFC dysfunction can lead to either impulsive states with increased tendency to initiate action 2 , or to amotivational states characterized by symptoms such as reduced activity, hopelessness and depressed mood 3 . Considering the opposite valence of these two phenotypes as well as the broad complexity of other tasks attributed to PFC, we sought to elucidate the PFC circuitry that favours effortful behavioural responses to challenging situations. Here we develop and use a quantitative method for the continuous assessment and control of active response to a behavioural challenge, synchronized with single-unit electrophysiology and optogenetics in freely moving rats. In recording from the medial PFC (mPFC), we observed that many neurons were not simply movement-related in their spike-firing patterns but instead were selectively modulated from moment to moment, according to the animal’s decision to act in a challenging situation. Surprisingly, we next found that direct activation of principal neurons in the mPFC had no detectable causal effect on this behaviour. We tested whether this