Improved dual-color GRAB sensors for monitoring dopaminergic activity in vivo

  • bioRxiv. 2023 Aug 25:2023.08.24.554559. doi: 10.1101/2023.08.24.554559.
Yizhou Zhuo  1  2  3 ,  Bin Luo  1  2  4  3 ,  Xinyang Yi  1  2 ,  Hui Dong  1  2  4 ,  Jinxia Wan  1  2  4 ,  Ruyi Cai  1  2 ,  John T Williams  5 ,  Tongrui Qian  1  2 ,  Malcolm G Campbell  6 ,  Xiaolei Miao  1  7 ,  Bozhi Li  1  8 ,  Yu Wei  1  2 ,  Guochuan Li  1  2 ,  Huan Wang  1  2 ,  Yu Zheng  1  2 ,  Mitsuko Watabe-Uchida  6 ,  Yulong Li  1  2  4  9  10  11
Affiliations
  • 1. State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China.
  • 2. PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
  • 3. These authors contributed equally.
  • 4. Peking-Tsinghua Center for Life Sciences, Beijing 100871, China.
  • 5. Vollum Institute, Oregon Health and Science University, Portland, OR 97239, USA.
  • 6. Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, 16 Divinity Avenue, Cambridge, MA 02138, USA.
  • 7. Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • 8. Department of Neurology, the First Medical Center, Chinese PLA General Hospital, Fuxing Road 28, Haidian District, Beijing 100853, China.
  • 9. Chinese Institute for Brain Research, Beijing 102206, China.
  • 10. Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518055, China.
  • 11. National Biomedical Imaging Center, Peking University, Beijing 100871, China.
PMID: 37662187 DOI: 10.1101/2023.08.24.554559
Abstract

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a vast network of dopaminergic projections. To fully dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent GPCR activation-based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity, and signal-to-noise properties with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in freely moving mice to measure both optogenetically evoked and behaviorally relevant DA release while measuring neurochemical signaling in the nucleus accumbens, amygdala, and cortex. Using these sensors, we also detected spatially resolved heterogeneous cortical DA release in mice performing various behaviors. These next-generation GRABDA sensors provide a robust set of tools for imaging dopaminergic activity under a variety of physiological and pathological conditions.

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