Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications
Understanding how neuronal activity patterns in the brain correlate with complex behavior is one of the primary goals of modern neuroscience. Chemical transmission is the major way of communication between neurons, however, traditional methods of detection of neurotransmitter and neuromodulator tran...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2019.00474/full |
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| author | Anna V. Leopold Daria M. Shcherbakova Vladislav V. Verkhusha Vladislav V. Verkhusha |
| author_facet | Anna V. Leopold Daria M. Shcherbakova Vladislav V. Verkhusha Vladislav V. Verkhusha |
| author_sort | Anna V. Leopold |
| collection | DOAJ |
| description | Understanding how neuronal activity patterns in the brain correlate with complex behavior is one of the primary goals of modern neuroscience. Chemical transmission is the major way of communication between neurons, however, traditional methods of detection of neurotransmitter and neuromodulator transients in mammalian brain lack spatiotemporal precision. Modern fluorescent biosensors for neurotransmitters and neuromodulators allow monitoring chemical transmission in vivo with millisecond precision and single cell resolution. Changes in the fluorescent biosensor brightness occur upon neurotransmitter binding and can be detected using fiber photometry, stationary microscopy and miniaturized head-mounted microscopes. Biosensors can be expressed in the animal brain using adeno-associated viral vectors, and their cell-specific expression can be achieved with Cre-recombinase expressing animals. Although initially fluorescent biosensors for chemical transmission were represented by glutamate biosensors, nowadays biosensors for GABA, acetylcholine, glycine, norepinephrine, and dopamine are available as well. In this review, we overview functioning principles of existing intensiometric and ratiometric biosensors and provide brief insight into the variety of neurotransmitter-binding proteins from bacteria, plants, and eukaryotes including G-protein coupled receptors, which may serve as neurotransmitter-binding scaffolds. We next describe a workflow for development of neurotransmitter and neuromodulator biosensors. We then discuss advanced setups for functional imaging of neurotransmitter transients in the brain of awake freely moving animals. We conclude by providing application examples of biosensors for the studies of complex behavior with the single-neuron precision. |
| first_indexed | 2024-12-10T19:30:20Z |
| format | Article |
| id | doaj.art-6774e016f19441b3b6e2fe30aa75de92 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-10T19:30:20Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-6774e016f19441b3b6e2fe30aa75de922022-12-22T01:36:16ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022019-10-011310.3389/fncel.2019.00474484896Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and ApplicationsAnna V. Leopold0Daria M. Shcherbakova1Vladislav V. Verkhusha2Vladislav V. Verkhusha3Medicum, Faculty of Medicine, University of Helsinki, Helsinki, FinlandDepartment of Anatomy and Structural Biology, Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, United StatesMedicum, Faculty of Medicine, University of Helsinki, Helsinki, FinlandDepartment of Anatomy and Structural Biology, Gruss-Lipper Biophotonics Center, Albert Einstein College of Medicine, Bronx, NY, United StatesUnderstanding how neuronal activity patterns in the brain correlate with complex behavior is one of the primary goals of modern neuroscience. Chemical transmission is the major way of communication between neurons, however, traditional methods of detection of neurotransmitter and neuromodulator transients in mammalian brain lack spatiotemporal precision. Modern fluorescent biosensors for neurotransmitters and neuromodulators allow monitoring chemical transmission in vivo with millisecond precision and single cell resolution. Changes in the fluorescent biosensor brightness occur upon neurotransmitter binding and can be detected using fiber photometry, stationary microscopy and miniaturized head-mounted microscopes. Biosensors can be expressed in the animal brain using adeno-associated viral vectors, and their cell-specific expression can be achieved with Cre-recombinase expressing animals. Although initially fluorescent biosensors for chemical transmission were represented by glutamate biosensors, nowadays biosensors for GABA, acetylcholine, glycine, norepinephrine, and dopamine are available as well. In this review, we overview functioning principles of existing intensiometric and ratiometric biosensors and provide brief insight into the variety of neurotransmitter-binding proteins from bacteria, plants, and eukaryotes including G-protein coupled receptors, which may serve as neurotransmitter-binding scaffolds. We next describe a workflow for development of neurotransmitter and neuromodulator biosensors. We then discuss advanced setups for functional imaging of neurotransmitter transients in the brain of awake freely moving animals. We conclude by providing application examples of biosensors for the studies of complex behavior with the single-neuron precision.https://www.frontiersin.org/article/10.3389/fncel.2019.00474/fullGPCRGltIGABAglutamatedopamineserotonin |
| spellingShingle | Anna V. Leopold Daria M. Shcherbakova Vladislav V. Verkhusha Vladislav V. Verkhusha Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications Frontiers in Cellular Neuroscience GPCR GltI GABA glutamate dopamine serotonin |
| title | Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications |
| title_full | Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications |
| title_fullStr | Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications |
| title_full_unstemmed | Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications |
| title_short | Fluorescent Biosensors for Neurotransmission and Neuromodulation: Engineering and Applications |
| title_sort | fluorescent biosensors for neurotransmission and neuromodulation engineering and applications |
| topic | GPCR GltI GABA glutamate dopamine serotonin |
| url | https://www.frontiersin.org/article/10.3389/fncel.2019.00474/full |
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