Dopamine plays a key role in motivation and reward. It has been proposed that dopamine neurons in the ventral tegmental area signal the discrepancy between expected and actual rewards (i.e., reward prediction error) while those in the substantia nigra pars compacta signal salience. Despite their importance, the mechanisms that regulate their activities remain elusive. In this talk, I will present our recent efforts toward understanding neural circuits that regulate dopamine neuron firing using a mouse model.