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  3. In vivo multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors

In vivo multiplex imaging of dynamic neurochemical networks with designed far-red dopamine sensors

  • bioRxiv. 2024 Dec 23:2024.12.22.629999. doi: 10.1101/2024.12.22.629999.
Yu Zheng 1 2,  Ruyi Cai 2 3,  Kui Wang 4,  Junwei Zhang 5,  Yizhou Zhuo 2 3,  Hui Dong 2 3,  Yuqi Zhang 3 6,  Yifan Wang 7,  Fei Deng 2 3,  En Ji 2 3,  Yiwen Cui 1 2,  Shilin Fang 4,  Xinxin Zhang 4,  Kecheng Zhang 5,  Jinxu Wang 3 8,  Guochuan Li 3,  Xiaolei Miao 3 8,  Zhenghua Wang 1 2,  Yuqing Yang 2 3,  Shaochuang Li 3,  Jonathan Grimm 9,  Kai Johnsson 6,  Eric Schreiter 9,  Luke Lavis 9,  Zhixing Chen 1 5 10,  Yu Mu 4 11,  Yulong Li 1 2 3 12 10
Affiliations

Affiliations

  • 1 Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Beijing 100871, China.
  • 2 PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
  • 3 State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China.
  • 4 Institute of Neuroscience, State Key Laboratory of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China.
  • 5 Institute of Molecular Medicine, Peking University College of Future Technology, Beijing 100871, China.
  • 6 Department of Chemical Biology, Max Planck Institute for Medical Research, Heidelberg 69120, Germany.
  • 7 Neuroscience Institute, New York University Langone Medical Center, New York 10016, USA.
  • 8 Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • 9 Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia 20147, USA.
  • 10 National Biomedical Imaging Center, Peking University, Beijing 100871, China.
  • 11 University of Chinese Academy of Sciences, Beijing 100049, China.
  • 12 Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518055, China.
PMID: 39763912 DOI: 10.1101/2024.12.22.629999
Abstract

Neurochemical signals like dopamine (DA) play a crucial role in a variety of brain functions through intricate interactions with Other neuromodulators and intracellular signaling pathways. However, studying these complex networks has been hindered by the challenge of detecting multiple neurochemicals in vivo simultaneously. To overcome this limitation, we developed a single-protein chemigenetic DA sensor, HaloDA1.0, which combines a cpHaloTag-chemical dye approach with the G protein-coupled receptor activation-based (GRAB) strategy, providing high sensitivity for DA, sub-second response kinetics, and an extensive spectral range from far-red to near-infrared. When used together with existing green and red fluorescent neuromodulator sensors, CA2+ indicators, cAMP sensors, and optogenetic tools, HaloDA1.0 provides high versatility for multiplex imaging in cultured neurons, brain slices, and behaving Animals, facilitating in-depth studies of dynamic neurochemical networks.

Keywords

dopamine; far-red; multiplex imaging; neurochemical; sensor.

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