Next-generation GRAB Sensors for Monitoring Dopaminergic Activity in Vivo

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2020 Oct 22

PMID 33087905

Citations 198

Authors

Fangmiao Sun

Jingheng Zhou

Bing Dai

Tongrui Qian

Jianzhi Zeng

Xuelin Li

Yizhou Zhuo

Yajun Zhang

Yipan Wang

Cheng Qian

Ke Tan

Jiesi Feng

Hui Dong

Dayu Lin

Guohong Cui

Yulong Li

Affiliations

Soon will be listed here.

Abstract

Dopamine (DA) plays a critical role in the brain, and the ability to directly measure dopaminergic activity is essential for understanding its physiological functions. We therefore developed red fluorescent G-protein-coupled receptor-activation-based DA (GRAB) sensors and optimized versions of green fluorescent GRAB sensors. In response to extracellular DA, both the red and green GRAB sensors exhibit a large increase in fluorescence, with subcellular resolution, subsecond kinetics and nanomolar-to-submicromolar affinity. Moreover, the GRAB sensors resolve evoked DA release in mouse brain slices, detect evoked compartmental DA release from a single neuron in live flies and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Coexpressing red GRAB with either green GRAB or the calcium indicator GCaMP6s allows tracking of dopaminergic signaling and neuronal activity in distinct circuits in vivo.

Citing Articles

An axonal brake on striatal dopamine output by cholinergic interneurons.

Zhang Y, Luan P, Qiao Q, He Y, Zatka-Haas P, Zhang G Nat Neurosci. 2025; .

PMID: 40082616 DOI: 10.1038/s41593-025-01906-5.

Dual neuromodulatory dynamics underlie birdsong learning.

Qi J, Schreiner D, Martinez M, Pearson J, Mooney R Nature. 2025; .

PMID: 40074907 DOI: 10.1038/s41586-025-08694-9.

Dopamine in the tail of the striatum facilitates avoidance in threat-reward conflicts.

Tsutsui-Kimura I, Tian Z, Amo R, Zhuo Y, Li Y, Campbell M Nat Neurosci. 2025; .

PMID: 40065189 DOI: 10.1038/s41593-025-01902-9.

Amphetamine in Adolescence Induces a Sex-Specific Mesolimbic Dopamine Phenotype in the Adult Prefrontal Cortex.

Hernandez G, Zhao J, Niu Z, MacGowan D, Capolicchio T, Song A bioRxiv. 2025; .

PMID: 40060609 PMC: 11888448. DOI: 10.1101/2025.02.26.640363.

Fiber photometry analysis of spontaneous dopamine signals: The z-scored data are not the data.

Wallace C, Slinkard C, Shaughnessy R, Holleran K, Centanni S, Lapish C bioRxiv. 2025; .

PMID: 40060421 PMC: 11888193. DOI: 10.1101/2025.02.19.639080.

References

Wise R . Dopamine, learning and motivation. Nat Rev Neurosci. 2004; 5(6):483-94. DOI: 10.1038/nrn1406. View

LARENG L, Virenque C . [Neuromuscular inhibition by antibiotics]. Therapie. 1968; 23(4):885-98. View

Miszalok V, Fritzsch T, WOLLENSAK J . Contrast echography of the eye and orbit. Ophthalmologica. 1986; 193(4):231-5. DOI: 10.1159/000309715. View

Kruss S, Salem D, Vukovic L, Lima B, Vander Ende E, Boyden E . High-resolution imaging of cellular dopamine efflux using a fluorescent nanosensor array. Proc Natl Acad Sci U S A. 2017; 114(8):1789-1794. PMC: 5338365. DOI: 10.1073/pnas.1613541114. View

Beyene A, Delevich K, Del Bonis-ODonnell J, Piekarski D, Lin W, Thomas A . Imaging striatal dopamine release using a nongenetically encoded near infrared fluorescent catecholamine nanosensor. Sci Adv. 2019; 5(7):eaaw3108. PMC: 6620097. DOI: 10.1126/sciadv.aaw3108. View

DANILOV A, Pershina L . [Cyclic nucleotides in muscarinic stimulation of the smooth muscles of the small intestine in the guinea pig]. Dokl Akad Nauk SSSR. 1984; 277(3):738-41. View

Gloor M, Reimus H, Wirth H . Cell-kinetic investigations on the epidermis of uninvolved skin of patients suffering from seborrheic eczema. Arch Dermatol Res. 1982; 272(1-2):139-41. DOI: 10.1007/BF00510404. View

Bernuzzi V, Desor D, Lehr P . Developmental alternations in offspring of female rats orally intoxicated by aluminum chloride or lactate during gestation. Teratology. 1989; 40(1):21-7. DOI: 10.1002/tera.1420400104. View

Alford S, Wu J, Zhao Y, Campbell R, Knopfel T . Optogenetic reporters. Biol Cell. 2012; 105(1):14-29. DOI: 10.1111/boc.201200054. View

10.

Zhao Y, Araki S, Wu J, Teramoto T, Chang Y, Nakano M . An expanded palette of genetically encoded Ca²⁺ indicators. Science. 2011; 333(6051):1888-91. PMC: 3560286. DOI: 10.1126/science.1208592. View

11.

Bindels D, Haarbosch L, van Weeren L, Postma M, Wiese K, Mastop M . mScarlet: a bright monomeric red fluorescent protein for cellular imaging. Nat Methods. 2016; 14(1):53-56. DOI: 10.1038/nmeth.4074. View

12.

Shemiakina I, Ermakova G, Cranfill P, Baird M, Evans R, Souslova E . A monomeric red fluorescent protein with low cytotoxicity. Nat Commun. 2012; 3:1204. DOI: 10.1038/ncomms2208. View

13.

Sung Y, Wilkins A, Rodriguez G, Wensel T, Lichtarge O . Intramolecular allosteric communication in dopamine D2 receptor revealed by evolutionary amino acid covariation. Proc Natl Acad Sci U S A. 2016; 113(13):3539-44. PMC: 4822589. DOI: 10.1073/pnas.1516579113. View

14.

Chien E, Liu W, Zhao Q, Katritch V, Han G, Hanson M . Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science. 2010; 330(6007):1091-5. PMC: 3058422. DOI: 10.1126/science.1197410. View

15.

Wu J, Liu L, Matsuda T, Zhao Y, Rebane A, Drobizhev M . Improved orange and red Ca²± indicators and photophysical considerations for optogenetic applications. ACS Chem Neurosci. 2013; 4(6):963-72. PMC: 3689190. DOI: 10.1021/cn400012b. View

16.

Pedelacq J, Cabantous S, Tran T, Terwilliger T, Waldo G . Engineering and characterization of a superfolder green fluorescent protein. Nat Biotechnol. 2005; 24(1):79-88. DOI: 10.1038/nbt1172. View

17.

St-Pierre F, Marshall J, Yang Y, Gong Y, Schnitzer M, Lin M . High-fidelity optical reporting of neuronal electrical activity with an ultrafast fluorescent voltage sensor. Nat Neurosci. 2014; 17(6):884-9. PMC: 4494739. DOI: 10.1038/nn.3709. View

18.

Hornblass A, Dolan R . Choroidal hematoma and proptosis following cataract surgery. Ann Ophthalmol. 1973; 5(11):1245-8. View

19.

Canale A, SARRA C, Cellino Tosi A, Boccignone M . [The total amount of saturated fatty acids and unsaturated fatty acids in postpartum cow's colostrum. The variations, during secretion, of the AGS/AGI indes]. Minerva Pediatr. 1966; 18(15):776-7. View

20.

Kroeze W, Sassano M, Huang X, Lansu K, McCorvy J, Giguere P . PRESTO-Tango as an open-source resource for interrogation of the druggable human GPCRome. Nat Struct Mol Biol. 2015; 22(5):362-9. PMC: 4424118. DOI: 10.1038/nsmb.3014. View