Brain-wide in vivo dopamine dynamics revealed with next generation dLights

The advent of dLight, a class of genetically encoded dopamine sensor, has significantlyadvanced our ability to monitor real-time dopamine dynamics in living animals. The success ofdLight1.3b with its superior dynamic ranges has prompted the development of subsequentiterations of this sensor to broaden the applicability of in vivo dopamine monitoring, particularlyin brain regions characterized by sparse dopaminergic signaling. In this study, we present asystematic and extensive in vivo characterization of novel dLight variants (dLight3.6 &dLight3.8) in comparison to the dLight1.3b parents sensor and control sensor (dLight0),assessing their performance in brain regions exhibiting both high and low levels of dopaminergicinput. To assess the performance of these variants, we systematically recorded their activity inkey brain regions, including the dorsal striatum, hippocampus, nucleus accumbens, amygdala, andprefrontal cortex. The experiments were designed to encompass a range of behavioralparadigms, such as operant reward-seeking behavior, fear conditioning, and optogeneticstimulation of dopamine neurons. Our findings highlight the enhanced sensitivity and dynamicrange of the new dLight variants. The results underscore the utility of these refined dLightvariants for capturing dynamic dopamine signaling across a spectrum of physiological andbehavioral conditions, laying the foundation for more precise investigations into the role ofdopamine in complex neural processes.