Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

被引:711
作者
Patriarchi, Tommaso [1 ]
Cho, Jounhong Ryan [2 ]
Merten, Katharina [3 ]
Howe, Mark W. [4 ,7 ]
Marley, Aaron [5 ]
Xiong, Wei-Hong [6 ]
Folk, Robert W. [3 ]
Broussard, Gerard Joey [1 ]
Liang, Ruqiang [1 ]
Jang, Min Jee [2 ]
Zhong, Haining [6 ]
Dombeck, Daniel [4 ]
von Zastrow, Mark [5 ]
Nimmerjahn, Axel [3 ]
Gradinaru, Viviana [2 ]
Williams, John T. [6 ]
Tian, Lin [1 ]
机构
[1] Univ Calif Davis, Dept Biochem & Mol Med, 2700 Stockton Blvd, Sacramento, CA 95817 USA
[2] CALTECH, Div Biol & Biol Engn, Pasadena, CA 91125 USA
[3] Salk Inst Biol Studies, Waitt Adv Biophoton Ctr, 10010 N Torrey Pines Rd, La Jolla, CA 92037 USA
[4] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA
[5] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94131 USA
[6] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA
[7] Boston Univ, Dept Psychol & Brain Sci, Boston, MA 02215 USA
关键词
VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; ADRENERGIC-RECEPTOR; ACTION INITIATION; REWARD; TRANSMISSION; RELEASE; NEUROMODULATION; PREDICTION; CIRCUITS;
D O I
10.1126/science.aat4422
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1420 / +
页数:9
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