“To learn, you must pay attention.” Molecular insights into teachers' wisdom

Abstract

The neuromodulator dopamine (DA) regulates a series of physiological functions in the brain from the control of locomotion, emotion, and affect, to mechanisms of reward and cognition. Neurons that synthesize DA originate mostly from 2 specialized areas of the basal ganglia, the substantia nigra and the ventral tegmental area and project, respectively, to the dorsal striatum to form the nigrostriatal pathway and the nucleus accumbens, amygdala, and hippocampus, as well as the frontal cortex to form the mesolimbic and mesocortical pathways (1). It has been established electrophysiologically that dopaminergic neurons characteristically exhibit 2 distinct modes of firing, a slow or tonic and a burst or phasic mode (2). Phasic firing of dopaminergic neurons has been shown to occur in response to cues that predict reward. Indeed, the activity of DA neurons follows the expectations of a prediction error that reflects the difference between predicted and delivered rewards (3). Neurochemical studies have shown that reward-predicting cues evoke DA concentration transients in terminal regions, the predicted outcome of phasic firing (4). Thus, a large body of evidence supports a central role for phasic DA release in reward-driven learning. However, it has been difficult to determine with certainty the trigger that initiates this phasic firing. Likewise, the behavioral roles of phasic and tonic firing of DA neurons have been unclear. Answers to these questions are emerging from a study in this issue of PNAS (5), in which burst firing and phasic release of DA are found to be associated only with cue-conditioned behaviors that predict reward or aversion. These findings imply that tonic firing of DA neurons is sufficient to mediate the large repertoire of behaviors normally attributed to DA.