Context-Dependent Multiplexing by Individual VTA Dopamine Neurons

Dopamine (DA) neurons of the VTA track cues and rewards to generate a reward prediction error signal during Pavlovian conditioning. Here we explored how these neurons respond to a self-paced, operant task in freely moving mice. The animal could trigger a reward-predicting cue by remaining in a specific location of an operant box for a brief time before moving to a spout for reward collection. VTA DA neurons were identified using DAT-Cre male mice that carried an optrode with minimal impact on the behavioral task. In vivo single-unit recordings revealed transient fast spiking responses to the cue and reward in correct trials, while for incorrect ones the activity paused, reflecting positive and negative error signals of a reward prediction. In parallel, a majority of VTA DA neurons simultaneously encoded multiple actions (e.g., movement velocity, acceleration, distance to goal, and licking) in sustained slow firing modulation. Applying a GLM, we show that such multiplexed encoding of rewarding and motor variables by individual DA neurons was only apparent while the mouse was engaged in the task. Downstream targets may exploit such goal-directed multiplexing of VTA DA neurons to adjust actions to optimize the task's outcome.SIGNIFICANCE STATEMENT VTA DA neurons code for multiple functions, including the reward prediction error but also motivation and locomotion. Here we show that about half of the recorded VTA DA neurons perform multiplexing: they exploit the phasic and tonic activity modes to encode, respectively, the cue/reward responses and motor parameters, most prominently when the mouse engages in a self-paced operand task. VTA non-DA neurons, by contrast, encode motor parameters regardless of task engagement.