An expanded palette of dopamine sensors for multiplex imaging in vivo

Tommaso Patriarchi, Ali Mohebi, Junqing Sun, Aaron Marley, Ruqiang Liang, Chunyang Dong, Kyle Puhger, Grace Or Mizuno, Carolyn M. Davis, Brian Wiltgen, Mark von Zastrow, Joshua D. Berke, Lin Tian

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
JournalNature Methods
DOIs
StateAccepted/In press - 2020

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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