Science 360, eaat4422 (2018)

The ability to track the effects of neuromodulators such as dopamine (DA) on their target neuronal circuits is critical for understanding neuronal functions such as learning and motor control. To enable monitoring of DA signaling with high temporal and spatial resolution, Patriarchi et al. developed DA sensors consisting of a circularly permuted GFP inserted into inert human DA receptors, such that DA-induced conformational changes were coupled to GFP fluorescence. Optimizing the dynamic range and affinity of the sensors through mutation, the authors obtained dLight1.1 and dLight1.2. The sensors could monitor the concentrations of released DA in response to electrical stimuli and with receptor modulators such as cocaine, which blocks DA reuptake. As well, the sensors could report on DA signals associated with a spatially intermingled, task-specific DA transients map in the cortex, locomotion in dorsal striatum, and temporally sensitive DA transients in freely moving mice in learning and behavioral assays. Overall, these tools can be used to dissect the spatiotemporal coding of DA in learning, decision-making, and motor control, which occurs in milliseconds and at a cellular level.

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