The role of glutamate receptor-dependent signaling in the dopamine system in reinforcement learning and adaptive decision-making
Midbrain dopamine (DA) neurons, together with the major target of their projections – dopaminoceptive neurons in the frontal cortex and basal ganglia, provide a neural substrate for reinforcement learning and are involved in decision-making and action selection. Activity and plasticity in the DA system is largely dependent on excitatory glutamatergic transmission. Here, we sought to determine the role of glutamate receptors in the DA system by using genetically modified mice with cell‑type specific ablation of NMDA or mGluR5 receptors in DA neurons and neurons expressing dopamine D1 receptors. Animals were tested in an adaptive decision-making task, that resembles a ‘two-armed bandit problem’, in which mouse is required to estimate by trial-and-error expected value of two alternatives associated with different reward probabilities (80% vs. 20%). During each session reward probabilities were reversed after 60 trials. In order to maximize the long-term sum of rewards, a mouse had to select alternative with higher success probability and adapt their choices to changes in reward contingencies. We observed that disruption of NMDA receptor-dependent signaling in DA neurons caused an initial impairment in error-driven learning and reduced the likelihood of returning to previously rewarded alternative. Moreover, loss of mGluR5 but not NMDA receptors in D1 receptor-expressing neurons decreased reward sensitivity, and as a consequence frequency of choosing alternative with higher reward probability. Finally, loss of NMDA receptors in DA neurons and mGluR5 receptors in D1 neurons caused a delay in decision time and increased latency to collect reward. In conclusion, our results suggest that glutamate receptor-dependent signaling in the DA system is necessary for quick and optimal decision-making. FINANCIAL SUPPORT: National Science Centre grant PRELUDIUM 2014/15/N/NZ4/00761.