Figure 3.

Pairing of functionally distinct dopaminergic sub-circuits. A salient external stimulus (blue arrow) can activate different pathways depending on the context and valence of the stimulus. We propose 3 different scenarios speculating on how the BG circuitry can be engaged to produce an appropriate and complex (reward and motor-based) behavioral response. (A) Upstream pairing scenario with a common input (e.g., GP) recruiting both VTA and SNc DA populations. When such a common input is activated, it synchronizes the DA release of VTA and SNc at their specific targets (mPFC and DS, respectively), hence recruiting these complementary pathways to engage both reward and motor programs for the execution of a task. (B) Local pairing via a so far unreported direct DA-DA interaction where the activation of one DA neuronal population induces the modulation of the other, hence engaging both complementary output pathways (mPFC and DS) to produce an elaborated behavioral outcome. (C) Downstream pairing scenario with mutual recruitment of output regions independently of the DA source. For example, the activation of VTA DA cells engages its specific output target (the mPFC) which itself activates the SNc DA neurons’ target (DS) independently of the release of DA from the SNc cells. Blue shading highlights the recruited regions for each scenario. Orange dotted shapes represent the location where the pairing occurs.