Abstract
Neurotransmitters and neuromodulators have a wide range of key roles throughout the nervous system. However, their dynamics in both health and disease have been challenging to assess, owing to the lack of in vivo tools to track them with high spatiotemporal resolution. Thus, developing a platform that enables minimally invasive, large-scale and long-term monitoring of neurotransmitters and neuromodulators with high sensitivity, high molecular specificity and high spatiotemporal resolution has been essential. Here, we review the methods available for monitoring the dynamics of neurotransmitters and neuromodulators. Following a brief summary of non-genetically encoded methods, we focus on recent developments in genetically encoded fluorescent indicators, highlighting how these novel indicators have facilitated advances in our understanding of the functional roles of neurotransmitters and neuromodulators in the nervous system. These studies present a promising outlook for the future development and use of tools to monitor neurotransmitters and neuromodulators.
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Acknowledgements
The authors thank all scientists whose studies were reviewed in this paper, and apologize to those whose work was not cited owing to space limitations. The authors thank the Li laboratory members for fruitful discussions. This research was supported by the Beijing Municipal Science & Technology Commission (Z181100001318002 and Z181100001518004), the National Natural Science Foundation of China (81821092), the National Key Research and Development Program of China (2020YFE0204000), the Feng Foundation of Biomedical Research, the Peking-Tsinghua Center for Life Sciences and the State Key Laboratory of Membrane Biology at Peking University School of Life Sciences (Y.L.); the US National Institutes of Health (NIH) Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative (NS103558; Y.L. and D.L.); the NIH (R01MH101377, 1R01HD092596 and U19NS107616; D.L.); and the Boehringer Ingelheim-Peking University Postdoctoral Program (Z.W.).
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Y.L. is listed as an inventor on a pending patent application filed by Peking University (international patent no. PCT/CN2018/107533), the value of which might be affected by this publication. The remaining authors declare no competing interests.
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Glossary
- Gliosis
-
The hypertrophy of glial cells.
- Voltammetry
-
An electrochemical method used to measure the concentration of neurochemicals by detecting the oxidation and reduction processes; signals are calculated in terms of applied potential.
- Amperometry
-
An electrochemical method used to measure the concentration of neurochemicals by detecting the oxidation and reduction processes; signals are determined at a fixed voltage.
- Cyclic voltammetry
-
A voltammetric method in which the current is measured while a linearly cycled potential is swept over the range of interest.
- Faradaic currents
-
Currents generated by the reduction or oxidation of a chemical substance at an electrode.
- Half-maximal effective concentration
-
(EC50). The concentration of a chemical (for example, dopamine (DA)) which induces a response halfway between the baseline and the maximum.
- Dynamic range
-
The ratio between the largest signal and the lowest one induced by neurochemicals.
- Site-saturation mutagenesis
-
A powerful mutagenesis strategy for protein engineering and directed evolution, which allows the substitution of predetermined protein sites against all 20 possible amino acids at once.
- ΔF/F 0
-
A commonly used equation to quantify the fluorescent intensity changes of fluorescent indicators, in which F is the signal trace from each detector and F0 is the fluorescence baseline.
- Ring neurons
-
Named for their circumferential ring-like axonal arborization patterns that form several circular laminae in the anterior shell of the ellipsoid body in Drosophila brain.
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Wu, Z., Lin, D. & Li, Y. Pushing the frontiers: tools for monitoring neurotransmitters and neuromodulators. Nat Rev Neurosci 23, 257–274 (2022). https://doi.org/10.1038/s41583-022-00577-6
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DOI: https://doi.org/10.1038/s41583-022-00577-6
