BMI Progress Reports 2021 // Prof. Sandi's Lab: Jun Huang - Changes in nucleus accumbens dopamine signals accompanying reward-based learning of a goal-directed sensorimotor transformation

Dopamine signals are thought to be important for reward-based learning and appear to play important roles in regulating synaptic plasticity in the nucleus accumbens and the striatum. However, the precise neuronal circuit mechanisms underlying the learning of even the simplest goal-directed sensorimotor transformations remain to be precisely defined. Here, we measured dopamine signals with fiber photometry using dLight expressed in the nucleus accumbens of head-restrained mice across reward-based sensorimotor task learning. Thirsty mice were first trained in a free-licking task, during which the mouse learned to lick a spout, for which they were sometimes rewarded with water delivery. In free licking sessions, reward triggered a positive dopamine signal, consistent with previous findings, while unrewarded licks evoked a negative dopamine signal. The amplitude of the reward-triggered dopamine response decreased across most individual sessions, likely reflecting the gradual reduction in thirst across each session with accumulated reward. Subsequently, the same mice were trained over days in a whisker-detection task, in which mice learned to lick the reward spout in response to a single brief whisker deflection. Reward delivery appeared to evoke a consistent dLight response across learning days. Whisker detection task learning was accompanied by an increase in a fast sensory-evoked dopamine signal, consistent with a large body of literature indicating dopaminergic reward prediction error signals. These dopamine reward-related signals could causally contribute to task-learning, for example through regulating synaptic plasticity at corticostriatal synapses. Interestingly, dopamine signal dynamics in individual mice during the free-licking task appeared to be predictive of performance on the first day of learning of the whisker detection task. Our results are thus consistent with a role of dopaminergic signalling in reward-based learning and further suggest that inter-individual differences in dopamine dynamics may be an early predictor of future learning performance. As a next step, it will be important to carry out pharmacological and optogenetic manipulations to test these hypotheses in further detail.