Electrophysiological evidence that a subset of midbrain dopamine neurons integrate the reward signal induced by electrical stimulation of the posterior mesencephalon.

This study was aimed at determining whether midbrain dopamine (DA) neurons are trans-synaptically activated by rewarding electrical stimulation applied near the midline in the posterior mesencephalon (PM), and in the affirmative, whether the increase in firing was proportional to the rewarding effectiveness of the stimulation. Experiments were performed on male Long-Evans rats trained to lever press to obtain 400 ms trains of cathodal rectangular pulses. Following the training period, curves relating the rates of responding to the stimulation frequencies were determined at two current intensities and reward thresholds were calculated for each animal. Each animal was then anesthetized with urethane (1.2 g/kg, i.p.) and firing rate of DA neurons were recorded before, during, and after each of 50 trains (1 train/3 s) of stimulation to the PM using stimulation parameters that either sustained near threshold responding (rewarding), or failed to sustain responding (non-rewarding), in the behavioral tests. A total of 24 DA cells were recorded from 13 behaviorally trained animals, and of these, 17 (71%) responded to rewarding stimulation by an increase in firing, five (21%) were unresponsive and two (8%) were inhibited. In 12 of the 17 cells that were activated, the increase in firing was proportional to the rewarding effectiveness of the stimulation rather than the total strength of the stimulation. These results provide evidence that a subset of midbrain DA neurons are trans-synaptically activated by rewarding PM stimulation and constitute a second, or subsequent, stage of the reward-relevant pathway that integrates the PM reward signal.