2. Academic Validation
  3. Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo

Improved green and red GRAB sensors for monitoring dopaminergic activity in vivo

  • Nat Methods. 2023 Nov 30. doi: 10.1038/s41592-023-02100-w.
Yizhou Zhuo # 1 2,  Bin Luo # 1 2 3,  Xinyang Yi 1 2,  Hui Dong 1 2 3,  Xiaolei Miao 1 2 4,  Jinxia Wan 1 2 3,  John T Williams 5,  Malcolm G Campbell 6,  Ruyi Cai 1 2,  Tongrui Qian 1 2,  Fengling Li 7,  Sophia J Weber 8,  Lei Wang 1 2 9,  Bozhi Li 1 2 10,  Yu Wei 1 2,  Guochuan Li 1 2,  Huan Wang 1 2,  Yu Zheng 1 2,  Yulin Zhao 1 2,  Marina E Wolf 8,  Yingjie Zhu 7,  Mitsuko Watabe-Uchida 6,  Yulong Li 11 12 13 14 15 16
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China.
  • 2 PKU-IDG/McGovern Institute for Brain Research, Beijing, China.
  • 3 Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Beijing, China.
  • 4 Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
  • 5 Vollum Institute, Oregon Health & Science University, Portland, OR, USA.
  • 6 Center for Brain Science, Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA, USA.
  • 7 Shenzhen Key Laboratory of Drug Addiction, Shenzhen Neher Neural Plasticity Laboratory, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China.
  • 8 Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
  • 9 Peking University-Tsinghua University-National Institute of Biological Sciences Joint Graduate Program, Peking University, Beijing, China.
  • 10 Department of Neurology, The First Medical Center, Chinese PLA General Hospital, Beijing, China.
  • 11 State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing, China. yulongli@pku.edu.cn.
  • 12 PKU-IDG/McGovern Institute for Brain Research, Beijing, China. yulongli@pku.edu.cn.
  • 13 Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Beijing, China. yulongli@pku.edu.cn.
  • 14 Chinese Institute for Brain Research, Beijing, China. yulongli@pku.edu.cn.
  • 15 Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, China. yulongli@pku.edu.cn.
  • 16 National Biomedical Imaging Center, Peking University, Beijing, China. yulongli@pku.edu.cn.
  • # Contributed equally.
PMID: 38036855 DOI: 10.1038/s41592-023-02100-w
Abstract

Dopamine (DA) plays multiple roles in a wide range of physiological and pathological processes via a large network of dopaminergic projections. To dissect the spatiotemporal dynamics of DA release in both dense and sparsely innervated brain regions, we developed a series of green and red fluorescent G-protein-coupled receptor activation-based DA (GRABDA) sensors using a variety of DA receptor subtypes. These sensors have high sensitivity, selectivity and signal-to-noise ratio with subsecond response kinetics and the ability to detect a wide range of DA concentrations. We then used these sensors in 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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