CaltechAUTHORS
  A Caltech Library Service

Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors

Patriarchi, Tommaso and Cho, Jounhong Ryan and Merten, Katharina and Howe, Mark W. and Marley, Aaron and Xiong, Wei-Hong and Folk, Robert W. and Broussard, Gerard Joey and Liang, Ruqiang and Jang, Min Jee and Zhong, Haining and Dombeck, Daniel and von Zastrow, Mark and Nimmerjahn, Axel and Gradinaru, Viviana and Williams, John T. and Tian, Lin (2018) Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. Science, 360 (6396). Art. No. eaat4422. ISSN 0036-8075. PMCID PMC6287765. https://resolver.caltech.edu/CaltechAUTHORS:20180601-103720713

[img] PDF - Accepted Version
See Usage Policy.

1183Kb
[img] PDF (Materials and Methods; Figs. S1 to S16; Captions for Data S1 to S3; References) - Supplemental Material
See Usage Policy.

10Mb
[img] PDF (Data S1 - Sequences of the constructs used in this study) - Supplemental Material
See Usage Policy.

112Kb
[img] MS Excel (Data S2 - Data info for Figure 1-2) - Supplemental Material
See Usage Policy.

507Kb
[img] MS Word (Data S3 - Data info for Figure 5) - Supplemental Material
See Usage Policy.

91Kb

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20180601-103720713

Abstract

Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires measuring spatiotemporally precise 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 striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1126/science.aat4422DOIArticle
https://www.sciencemag.org/cgi/content/full/science.aat4422/DC1PublisherSupplementary Materials
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6287765PubMed CentralArticle
ORCID:
AuthorORCID
Patriarchi, Tommaso0000-0001-9351-3734
Cho, Jounhong Ryan0000-0001-9542-716X
Merten, Katharina0000-0002-0197-0186
Broussard, Gerard Joey0000-0003-1636-2615
Liang, Ruqiang0000-0002-3075-4554
Jang, Min Jee0000-0002-1536-7177
von Zastrow, Mark0000-0003-1375-6926
Nimmerjahn, Axel0000-0002-0875-7855
Gradinaru, Viviana0000-0001-5868-348X
Tian, Lin0000-0001-7012-6926
Additional Information:© 2018 American Association for the Advancement of Science. Received 4 March 2018; accepted 17 May 2018. Published online 31 May 2018. We thank Brian Paul McGrew for assistance during in vitro sensor library screening and Huaiyang Cheng for producing AAV virus. Luke Lavis (Janelia Research Campus) kindly provide us NV-caged DA. Erin Carey performed cortical viral vector injections. Dr. Brett Mensh provided critical advice for writing and revising the manuscript. This project was made possible with generous help from Dr. Loren Looger (HHMI Janelia Research Campus). This work was supported by funding to L.T. (BRAIN Inititiave U01NS090604 and U01NS013522, DP2MH107056 from National Institute of Health), to A.N. (DP2NS083038, R01NS085938, P30CA014195), J.W., and M.V.Z (BRAIN Initiative U01NS013522 from National Institute of Health), to H.Z. (BRAIN Initiative U01NS094247 and R01NS104944), to D.D. (1R01MH110556 from National Institute of Health), and to V.G. (NIH DP2NS087949, NIH/NIA R01AG047664). K.M. is a DFG research fellow and recipient of a Catharina Foundation postdoctoral scholar award. V.G. is a Heritage Principal Investigator supported by the Heritage Medical Research Institute. Author contributions: L.T. and T.P conceived the project. T.P. and L.T. designed, screened and optimized sensors and characterized them in mammalian cells and cultured neurons. R.L. simulated structure of the sensor. A.M. and M.V.Z. characterized signaling properties of the sensor. W-H. X. and H.Z. characterized the sensor in organotypic brain slices. J.W. performed characterization in acute brain slices. M.H. and D.D. characterized the sensor in vivo in the dorsal striatum. J.R.C. and V.G. performed fiber photometry recordings coupled with optogenetic manipulations, calcium imaging and behavioral experiments in NAc, analyzed the data and prepared the related figures and text. M.J.J. performed hybridization chain reaction experiments and prepared relevant figures and text with input from J.R.C and V.G. K.M., R.F. and A. N. performed the two-photon imaging experiments in the cortex of behaving mice, analyzed the data and prepared the related figures and text. All authors analyzed the data. L.T. led the project. L.T., T.P. wrote the paper with contributions from all authors. Competing interests: L.T., R.L. and T.P. submitted a provisional patent application on sensor engineering. Data and materials availability: All DNA and viruses have been deposited in NCBI (accession number MH244549-MH244561), ADDGENE and The University of Pennsylvania Vector Core. All DNA plasmids and virus are available from UC Davis or designated repository under a material transfer agreement. Computer codes are deposited in github (https://github.com/GradinaruLab/dLight1/). All other data needed to evaluate the conclusion in the paper are present in the paper or the supplementary materials.
Group:Heritage Medical Research Institute
Funders:
Funding AgencyGrant Number
NIHU01NS090604
NIHU01NS013522
NIHDP2MH107056
NIHDP2NS083038
NIHR01NS085938
NIHP30CA014195
NIHU01NS013522
NIHU01NS094247
NIHR01NS104944
NIH1R01MH110556
NIHDP2NS087949
NIHR01AG047664
Catharina StichtingUNSPECIFIED
Heritage Medical Research InstituteUNSPECIFIED
Issue or Number:6396
PubMed Central ID:PMC6287765
Record Number:CaltechAUTHORS:20180601-103720713
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20180601-103720713
Official Citation:Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors. BY TOMMASO PATRIARCHI, JOUNHONG RYAN CHO, KATHARINA MERTEN, MARK W. HOWE, AARON MARLEY, WEI-HONG XIONG, ROBERT W. FOLK, GERARD JOEY BROUSSARD, RUQIANG LIANG, MIN JEE JANG, HAINING ZHONG, DANIEL DOMBECK, MARK VON ZASTROW, AXEL NIMMERJAHN, VIVIANA GRADINARU, JOHN T. WILLIAMS, LIN TIAN. SCIENCE 29 JUN 2018
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:86740
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:01 Jun 2018 18:14
Last Modified:09 Mar 2020 13:19

Repository Staff Only: item control page