Editorial: Neural Circuitry of Behavioral Flexibility: Dopamine and Related Systems

Dopamine neurotransmission has long been identified as a key component of prefrontal cortical function and flexible cognition; however, flexible behavior does not depend solely on dopamine. Together, multiple systems allow fast and flexible behavior in the face of a constantly changing environment. This Research Topic illuminates work by researchers who are leading efforts to understand how different neural systems yield flexible behavior. The psychostimulant amphetamine is, paradoxically, a useful treatment for Attention Deficit Hyperactivity Disorder (ADHD) symptoms. Here, Yen and colleagues demonstrate in a mouse model of ADHD that the calming effect of amphetamine is due to decreased GSK3B, initiated through NMDA receptor signaling (Yen et al.). Stress is known to be under the partial regulation of oxytocin, and oxytocin levels in adults may be influenced by severity of childhood maltreatment. The inconsistent quality of results on this topic are tackled by Mizuki and Fujiwara, who were able to demonstrate a correlation of severity of childhood maltreatment with diminishing oxytocin levels in humans (Mizuki and Fujiwara). A key challenge in combatting drug addiction is the incentive motivational property of a stimulus. This is known to develop through Pavlovian Instrumental Transfer (PIT). Garofalo and di Pellegrino were able to show, for the first time in humans, that Sign-Tracker responses were biased by reward-paired cues while Goal-Trackers were not (Garofalo and di Pellegrino). This information is critical in developing individualized treatment plans for treating maladaptive behaviors. Physical exercise is known to promote better cognition, but the mechanism remains unknown. In their article Berse and colleagues identified a particular single nucleotide polymorphism in the Dopamine Transporter (DAT1/SLCA6A3) gene which contributed to improved cognition under physical exercise conditions in adolescent humans (Berse et al.). These data suggest the usefulness in physical exercise to promote improved flexible cognition in adolescents. Altered neurochemistry in the anterior cingulate cortex (ACC) is thought to be a root cause of the behavioral symptoms of ADHD. However, when Endres and colleagues conducted a large single voxel proton scale magnetic resonance spectroscopy study, they identified no neurometabolic differences in ACC or cerebellum between control and experimental groups (Endres et al.). These results fail to replicate an earlier and smaller experiment, and the authors propose that the difficulty in diagnosing ADHD may lie in a number of false-negative studies. Flexible behavior is known to depend on the medial prefrontal cortex (mPFC). Bissonette and Roesch demonstrate how neural correlates of rules and conflict …