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Science. 2018 Jun 29;360(6396). pii: eaat4422. doi: 10.1126/science.aat4422. Epub 2018 May 31.

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors.

Author information

1
Department of Biochemistry and Molecular Medicine, University of California, Davis, 2700 Stockton Boulevard, Sacramento, CA 95817, USA.
2
Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
3
Waitt Advanced Biophotonics Center, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
4
Department of Neurobiology, Northwestern University, Evanston, IL 60208, USA.
5
Department of Cellular and Molecular Pharmacology, University of California, San Francisco, CA 94131, USA.
6
Vollum Institute, Oregon Health & Science University, Portland, OR 97239, USA.
7
Department of Biochemistry and Molecular Medicine, University of California, Davis, 2700 Stockton Boulevard, Sacramento, CA 95817, USA. lintian@ucdavis.edu.

Abstract

Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires spatiotemporally precise measurement of neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in mouse striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in mouse cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators.

Comment in

PMID:
29853555
PMCID:
PMC6287765
DOI:
10.1126/science.aat4422
[Indexed for MEDLINE]
Free PMC Article

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