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A neural circuit mechanism for encoding aversive stimuli in the mesolimbic dopamine system. A genetically encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice. Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. By enabling multiplexed imaging of dopamine with other circuit components in vivo, RdLight1 opens avenues for understanding many aspects of dopamine biology.

Dual-color photometry revealed that dopamine release in the nucleus accumbens evoked by reward-predictive cues is accompanied by a rapid suppression of glutamate release. We demonstrate the utility of RdLight1 for receptor-specific pharmacological analysis in cell culture, simultaneous assessment of dopamine release and cell-type-specific neuronal activity and simultaneous subsecond monitoring of multiple neurotransmitters in freely behaving rats. RdLight1 can be combined with GFP-based sensors with minimal interference and shows high photostability, permitting prolonged continuous imaging.

We therefore engineered red-shifted variants of dopamine sensors called RdLight1, based on mApple. However, these GFP-based variants cannot be readily combined with commonly used optical sensors and actuators, due to spectral overlap. Genetically encoded dopamine sensors based on green fluorescent protein (GFP) enable high-resolution imaging of dopamine dynamics in behaving animals.
