The timing of action determines reward prediction signals in identified midbrain dopamine neurons

Animals adapt behavior in response to informative sensory cues using multiple brain circuits. The activity of midbrain dopamine (mDA) neurons is thought to convey a critical teaching signal: reward prediction error (RPE). Although RPE signals are thought to be essential to learning, little is known about the dynamic changes in mDA neuron activity as animals learn about novel sensory cues and appetitive rewards. Here we describe a large dataset of cell-attached recordings of identified dopaminergic neurons as naïve mice learned a novel cue-reward association. During learning mDA neuron activity results from summation of sensory cue-related and movement initiation-related response components. These components are both a function of reward expectation yet dissociable. Learning produces an increasingly precise coordination of action initiation following sensory cues that results in apparent RPE correlates. Our data thus provide new insights into circuit mechanisms underlying a critical computation in a highly conserved learning circuit.