How conditioned stimuli acquire the ability to activate VTA dopamine cells: a proposed neurobiological component of reward-related learning

The ability to learn about conditioned stimuli (CS) associated with rewards is a crucial adaptive mechanism. Activity in the mesocorticolimbic dopamine (DA) system, as well as in the ventral tegmental area (VTA), is correlated with responding to and learning about CSs. The mechanism by which VTA neurons become activated by signals associated with conditioned stimuli is not fully understood. Our model suggests that NMDA receptor stimulation in the VTA allows originally weak glutamate signals carrying information about environmental stimuli, coincident with strong excitation correlated with primary rewards, to be strengthened and thereby acquire the ability to activate VTA neurons in themselves, producing approach. Furthermore, once synaptic strengthening occurs, the model suggests that NMDA receptor stimulation in VTA is not necessary for the expression of reward-related learning. In this review we survey evidence that VTA cells respond to cues associated with primary rewards, that this responding is acquired, and that the VTA possesses the attributes to function as a site of integration of signals of primary and conditioned stimuli.