2. Academic Validation
  3. Monitoring norepinephrine release in vivo using next-generation GRABNE sensors

Monitoring norepinephrine release in vivo using next-generation GRABNE sensors

  • Neuron. 2024 Mar 26:S0896-6273(24)00155-7. doi: 10.1016/j.neuron.2024.03.001.
Jiesi Feng 1,  Hui Dong 2,  Julieta E Lischinsky 3,  Jingheng Zhou 4,  Fei Deng 5,  Chaowei Zhuang 6,  Xiaolei Miao 7,  Huan Wang 5,  Guochuan Li 8,  Ruyi Cai 8,  Hao Xie 6,  Guohong Cui 4,  Dayu Lin 3,  Yulong Li 9
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China. Electronic address: [email protected].
  • 2 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 3 Neuroscience Institute, New York University School of Medicine, New York, NY 10016, USA.
  • 4 Neurobiology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.
  • 5 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
  • 6 Department of Automation, Tsinghua University, Beijing 100084, China.
  • 7 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, 100020 Beijing, China.
  • 8 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China.
  • 9 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China; PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China; Chinese Institute for Brain Research, Beijing 102206, China; Institute of Molecular Physiology, Shenzhen Bay Laboratory, Shenzhen, Guangdong 518055, China; National Biomedical Imaging Center, Peking University, Beijing 100871, China. Electronic address: [email protected].
PMID: 38547869 DOI: 10.1016/j.neuron.2024.03.001
Abstract

Norepinephrine (NE) is an essential biogenic monoamine neurotransmitter. The first-generation NE sensor makes in vivo, real-time, cell-type-specific and region-specific NE detection possible, but its low NE sensitivity limits its utility. Here, we developed the second-generation GPCR-activation-based NE sensors (GRABNE2m and GRABNE2h) with a superior response and high sensitivity and selectivity to NE both in vitro and in vivo. Notably, these sensors can detect NE release triggered by either optogenetic or behavioral stimuli in freely moving mice, producing robust signals in the locus coeruleus and hypothalamus. With the development of a novel transgenic mouse line, we recorded both NE release and calcium dynamics with dual-color fiber photometry throughout the sleep-wake cycle; moreover, dual-color mesoscopic imaging revealed cell-type-specific spatiotemporal dynamics of NE and calcium during sensory processing and locomotion. Thus, these new GRABNE sensors are valuable tools for monitoring the precise spatiotemporal release of NE in vivo, providing new insights into the physiological and pathophysiological roles of NE.

Keywords

GRAB; dual-color imaging; fluorescent sensors; in vivo imaging; mesoscopic imaging; neuromodulation; norepinephrine; transgenic mouse line.

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