학술논문

An expanded palette of dopamine sensors for multiplex imaging in vivo
Document Type
article
Source
Nature Methods. 17(11)
Subject
Biological Sciences
Bioengineering
Brain Disorders
Biotechnology
Neurosciences
Animals
Behavior
Animal
Biosensing Techniques
Brain
Cues
Dopamine
Green Fluorescent Proteins
HEK293 Cells
Humans
Neurons
Receptors
Dopamine
Reward
Technology
Medical and Health Sciences
Developmental Biology
Biological sciences
Language
Abstract
Genetically encoded dopamine sensors based on green fluorescent protein (GFP) enable high-resolution imaging of dopamine dynamics in behaving animals. However, these GFP-based variants cannot be readily combined with commonly used optical sensors and actuators, due to spectral overlap. We therefore engineered red-shifted variants of dopamine sensors called RdLight1, based on mApple. RdLight1 can be combined with GFP-based sensors with minimal interference and shows high photostability, permitting prolonged continuous imaging. 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. 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. By enabling multiplexed imaging of dopamine with other circuit components in vivo, RdLight1 opens avenues for understanding many aspects of dopamine biology.