Dopamine Modulation of Prefrontal Cortex Activity Is Manifold and Operates at Multiple Temporal and Spatial Scales.

Although the function of dopamine in subcortical structures is largely limited to reward and movement, dopamine neurotransmission in the prefrontal cortex (PFC) is critical to a multitude of temporally and functionally diverse processes, such as attention, working memory, behavioral flexibility, action planning, and sustained motivational and affective states. How does dopamine influence computation of these temporally complex functions? We find causative links between sustained and burst patterns of phasic dopamine neuron activation and modulation of medial PFC neuronal activity at multiple spatiotemporal scales. These include a multidirectional and weak impact on individual neuron rate activity but a robust influence on coordinated ensemble activity, gamma oscillations, and gamma-theta coupling that persisted for minutes. In addition, PFC network responses to burst pattern of dopamine firing were selectively strengthened in behaviorally active states. This multiplex mode of modulation by dopamine input may enable PFC to compute and generate spatiotemporally diverse and specialized outputs.