Convergent Processing Of Both Positive And Negative Motivational Signals By The VTA Dopamine Neuron

Dopamine neurons in the ventral tegmental area (VTA) have been traditionally studied for their roles in reward-related motivation or drug addiction. Electrophysiology studies have mainly examined how the dopamine neurons would respond to external conditioned or unconditioned stimuli. By using multi-tetrode extracellular recording in the VTA of freely behaving mice,1) we study how the VTA dopamine neurons may process both positive and negative motivational experiences. We find that the majority of the putative dopamine neurons in the VTA exhibit significant activation in response to the conditioned tone that predicts food reward, while the same dopamine neurons exhibit suppression and offset-excitation in response to fearful experiences such as free fall and shake. Importantly, VTA putative dopamine neurons exhibit the temporal dynamic activity:their firing change durations are proportional to the fearful event durations. Moreover, VTA putative dopamine neurons can bi-directionally respond to the same conditioned tone when it has different meanings in distinct contexts, which suggests that VTA dopamine neurons may employ the convergent encoding strategy with integration of cues and environmental context for processing both positive and negative experiences.2) We also study how the VTA dopamine neurons would react during internal motivation and internally guided actions. Mice are engaged in effort-based reward-seeking or aversion-escaping tasks in which they need to jump on a platform to get food reward (food-motivated jump) or jump out of an aversive chamber to escape from it (escape-motivated jump). Our results reveal that the VTA putative dopamine neurons exhibit uniform burst activation at the initiation of both reward-and escape-motivated jumping behaviors. Moreover, dopamine neurons exhibit effort-based levels of activation: their firing changes are proportional to the heights of the jumps. Similarly, dopamine neurons exhibit higher levels of activation in successful jumps in compare with the failed attempted jumps. The timing of the jump initiation is internally guided and completely voluntary, therefore, we suggest that the burst activation of the VTA dopamine neuron at jump initiation represents an internal motivational signal that is associated with expected positive or better outcomes. Taken together, our results suggest that VTA dopamine neurons may employ the convergent encoding strategy with integration of cues and environmental context for processing both internally and externally associated positive and negative motivational signals.