THE ROLE OF RIM1/2 PROTEINS IN EVOKED DOPAMINE RELEASE

Dopamine (DA) is a critical regulator of movement, motivation, and learning, but how one neurotransmitter can regulate such disparate functions is unknown. One hypothesis suggests that timing and patterns of neurotransmitter release may dissociate DA as a teaching signal from DA as a movement signal. Recent work indicates that RIM1/2 proteins are critical for phasic DA release, which could provide a unique opportunity to test how discrete patterns of DA signaling contribute to discrete behaviours. We trained mice lacking RIM1/2 protein in DA neurons (RIMKO-DA) on a battery of learning and motivational tasks while using fiber photometry to record striatal DA. We found that, contrary to previous reports, phasic DA release is present in RIMKO-DA mice, but with altered release kinetics. We sought to parameterize this alteration by measuring striatal DA with fiber photometry while optogenetically stimulating midbrain DA neurons at different frequencies and durations. We found that in vivo RIMKO-DA desynchronizes neurotransmitter release resulting in lower amplitude DA transients and a delayed return to baseline DA but that these alterations do not affect learning or motivation. Moreover, the effect of RIMKO on DA release is regionally dependent, where amplitude is blunted primarily in the dorsal striatum, while the return to baseline is delayed primarily in the nucleus accumbens. This work demonstrates that RIM1/2 are important for enabling proper timing of stimulus-evoked DA release but not critical for release in general or for facilitating normal behaviour.