2. Academic Validation
  3. Red-shifted GRAB acetylcholine sensors for multiplex imaging in vivo

Red-shifted GRAB acetylcholine sensors for multiplex imaging in vivo

  • bioRxiv. 2024 Dec 23:2024.12.22.627112. doi: 10.1101/2024.12.22.627112.
Shu Xie 1 2 3 4,  Xiaolei Miao 1 2 5 4,  Guochuan Li 1 2 3 4,  Yu Zheng 1 2 3,  Mengyao Li 1 2,  En Ji 1 2 3,  Jinxu Wang 1 2 5,  Shaochuang Li 1 2 3,  Ruyi Cai 1 2,  Lan Geng 1 2,  Jiesi Feng 1 2 3,  Changwei Wei 5,  Yulong Li 1 2 3 6 7
Affiliations

Affiliations

  • 1 State Key Laboratory of Membrane Biology, School of Life Sciences, Peking University, Beijing 100871, China.
  • 2 PKU-IDG/McGovern Institute for Brain Research, Beijing 100871, China.
  • 3 Peking-Tsinghua Center for Life Sciences, New Cornerstone Science Laboratory, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China.
  • 4 These authors contributed equally.
  • 5 Department of Anesthesiology, Beijing Chaoyang Hospital, Capital Medical University, Beijing 100020, China.
  • 6 Chinese Institute for Brain Research, Beijing 102206, China.
  • 7 National Biomedical Imaging Center, Peking University, Beijing 100871, China.
PMID: 39763957 DOI: 10.1101/2024.12.22.627112
Abstract

The neurotransmitter acetylcholine (ACh) is essential in both the central and peripheral nervous systems. Recent studies highlight the significance of interactions between ACh and various neuromodulators in regulating complex behaviors. The ability to simultaneously image ACh and Other neuromodulators can provide valuable information regarding the mechanisms underlying these behaviors. Here, we developed a series of red fluorescent G protein-coupled receptor activation-based (GRAB) ACh sensors, with a wide detection range and expanded spectral profile. The high-affinity sensor, rACh1h, reliably detects ACh release in various brain regions, including the nucleus accumbens, amygdala, hippocampus, and cortex. Moreover, rACh1h can be co-expressed with green fluorescent sensors in order to record ACh release together with Other neurochemicals in various behavioral contexts using fiber photometry and two-photon imaging, with high spatiotemporal resolution. These new ACh sensors can therefore provide valuable new insights regarding the functional role of the cholinergic system under both physiological and pathological conditions.

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