UC San Diego

In their pioneering study on dopamine release, Romo and Schultz speculated "...that the amount of dopamine released by unmodulated spontaneous impulse activity exerts a tonic, permissive influence on neuronal processes more actively engaged in preparation of self-initiated movements...."¹ Motivated by the suggestion of "spontaneous impulses," as well as by the "ramp up" of dopaminergic neuronal activity that occurs when rodents navigate to a reward,^2-5 we asked two questions. First, are there spontaneous impulses of dopamine that are released in cortex? Using cell-based optical sensors of extrasynaptic dopamine, [DA]_ex,⁶ we found that spontaneous dopamine impulses in cortex of naive mice occur at a rate of ∼0.01 per second. Next, can mice be trained to change the amplitude and/or timing of dopamine events triggered by internal brain dynamics, much as they can change the amplitude and timing of dopamine impulses based on an external cue?^7-9 Using a reinforcement learning paradigm based solely on rewards that were gated by feedback from real-time measurements of [DA]_ex, we found that mice can volitionally modulate their spontaneous [DA]_ex. In particular, by only the second session of daily, hour-long training, mice increased the rate of impulses of [DA]_ex, increased the amplitude of the impulses, and increased their tonic level of [DA]_ex for a reward. Critically, mice learned to reliably elicit [DA]_ex impulses prior to receiving a reward. These effects reversed when the reward was removed. We posit that spontaneous dopamine impulses may serve as a salient cognitive event in behavioral planning.