A role for Dopamine neuron NMDA receptors in learning and decision-making

Abstract

Midbrain dopamine has demonstrated roles in locomotion, motivation, associative learning, habit formation, action selection and cognition. The many functions of dopamine can be attributed to the multiple projection targets of midbrain dopaminergic nuclei and to the multiple characteristic modes of dopamine neuron firing, tonic and phasic. Phasic transients of midbrain dopamine neurons are widely reported to signal errors conveying discrepancies between predicted and actual reward. Knocking out NMDARs in dopamine neurons has been shown to attenuate dopaminergic phasic firing providing a potential model for delineating the functions of tonic and phasic dopamine. In order to study the role of dopamine neuron NMDARs in rewardcontingent learning, we developed an auditory-cued binary choice task using complex auditory stimuli that lend themselves to efficient learning as well as morphing. We report that mice lacking NMDARs in dopamine neurons have a deficit in learning an auditory two-alternative choice task, in the absence of changes in response vigor. Dopamine neurons respond phasically to rewards as well as reward predictive cues. Updating the reward predictive value of cues is fundamental to shaping adaptive patterns of behavior and decision-making. Given the hypothesized role of dopamine in the updating of reward predictive cues, we were interested to see if an influence of reward history would be evident in the choices made by mice lacking dopamine neuron NMDARs. In an auditory-cued binary choice task, we find an influence of the difficulty of prior successes on subsequent decisions when mice are challenged with varying degrees of discrimination difficulty. In mice lacking dopamine neuron NMDARs, we find a lack of influence of prior decision difficulty. Our results identify a modulation of choices by prior decision difficulty in mice, and demonstrate the dopamine-dependent nature of this modulation. These findings are consistent with a role for dopamine neuron phasic firing in the trial-by-trial shaping of reward contingent learning.