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Fast and sensitive GCaMP calcium indicators for imaging neural populations

Author

Listed:
  • Yan Zhang

    (Howard Hughes Medical Institute)

  • Márton Rózsa

    (Howard Hughes Medical Institute
    Allen Institute for Neural Dynamics)

  • Yajie Liang

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute
    University of Maryland School of Medicine)

  • Daniel Bushey

    (Howard Hughes Medical Institute)

  • Ziqiang Wei

    (Howard Hughes Medical Institute)

  • Jihong Zheng

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Daniel Reep

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Gerard Joey Broussard

    (Neuroscience Institute, Princeton University)

  • Arthur Tsang

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Getahun Tsegaye

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Sujatha Narayan

    (Howard Hughes Medical Institute
    Allen Institute for Neural Dynamics)

  • Christopher J. Obara

    (Howard Hughes Medical Institute)

  • Jing-Xuan Lim

    (Howard Hughes Medical Institute)

  • Ronak Patel

    (Howard Hughes Medical Institute)

  • Rongwei Zhang

    (Howard Hughes Medical Institute)

  • Misha B. Ahrens

    (Howard Hughes Medical Institute)

  • Glenn C. Turner

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Samuel S.-H. Wang

    (Neuroscience Institute, Princeton University)

  • Wyatt L. Korff

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Eric R. Schreiter

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Karel Svoboda

    (Howard Hughes Medical Institute
    Allen Institute for Neural Dynamics
    Howard Hughes Medical Institute)

  • Jeremy P. Hasseman

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Ilya Kolb

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute)

  • Loren L. Looger

    (Howard Hughes Medical Institute
    Howard Hughes Medical Institute
    University of California, San Diego)

Abstract

Calcium imaging with protein-based indicators1,2 is widely used to follow neural activity in intact nervous systems, but current protein sensors report neural activity at timescales much slower than electrical signalling and are limited by trade-offs between sensitivity and kinetics. Here we used large-scale screening and structure-guided mutagenesis to develop and optimize several fast and sensitive GCaMP-type indicators3–8. The resulting ‘jGCaMP8’ sensors, based on the calcium-binding protein calmodulin and a fragment of endothelial nitric oxide synthase, have ultra-fast kinetics (half-rise times of 2 ms) and the highest sensitivity for neural activity reported for a protein-based calcium sensor. jGCaMP8 sensors will allow tracking of large populations of neurons on timescales relevant to neural computation.

Suggested Citation

  • Yan Zhang & Márton Rózsa & Yajie Liang & Daniel Bushey & Ziqiang Wei & Jihong Zheng & Daniel Reep & Gerard Joey Broussard & Arthur Tsang & Getahun Tsegaye & Sujatha Narayan & Christopher J. Obara & Ji, 2023. "Fast and sensitive GCaMP calcium indicators for imaging neural populations," Nature, Nature, vol. 615(7954), pages 884-891, March.
    • Handle: RePEc:nat:nature:v:615:y:2023:i:7954:d:10.1038_s41586-023-05828-9
    DOI: 10.1038/s41586-023-05828-9
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    Cited by:

    1. Yuting Li & Zongyue Cheng & Chenmao Wang & Jianian Lin & Hehai Jiang & Meng Cui, 2024. "Geometric transformation adaptive optics (GTAO) for volumetric deep brain imaging through gradient-index lenses," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    2. Eiji Shigetomi & Hideaki Suzuki & Yukiho J. Hirayama & Fumikazu Sano & Yuki Nagai & Kohei Yoshihara & Keisuke Koga & Toru Tateoka & Hideyuki Yoshioka & Youichi Shinozaki & Hiroyuki Kinouchi & Kenji F., 2024. "Disease-relevant upregulation of P2Y1 receptor in astrocytes enhances neuronal excitability via IGFBP2," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    3. Marie A. Labouesse & Arturo Torres-Herraez & Muhammad O. Chohan & Joseph M. Villarin & Julia Greenwald & Xiaoxiao Sun & Mysarah Zahran & Alice Tang & Sherry Lam & Jeremy Veenstra-VanderWeele & Clay O., 2023. "A non-canonical striatopallidal Go pathway that supports motor control," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Camille Mazo & Margarida Baeta & Leopoldo Petreanu, 2024. "Auditory cortex conveys non-topographic sound localization signals to visual cortex," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    5. Yusuke Nasu & Abhi Aggarwal & Giang N. T. Le & Camilla Trang Vo & Yuki Kambe & Xinxing Wang & Felix R. M. Beinlich & Ashley Bomin Lee & Tina R. Ram & Fangying Wang & Kelsea A. Gorzo & Yuki Kamijo & Ma, 2023. "Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Caio Vaz Rimoli & Claudio Moretti & Fernando Soldevila & Enora Brémont & Cathie Ventalon & Sylvain Gigan, 2024. "Demixing fluorescence time traces transmitted by multimode fibers," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Aniruddha Das & Sarah Holden & Julie Borovicka & Jacob Icardi & Abigail O’Niel & Ariel Chaklai & Davina Patel & Rushik Patel & Stefanie Kaech Petrie & Jacob Raber & Hod Dana, 2023. "Large-scale recording of neuronal activity in freely-moving mice at cellular resolution," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    8. Maximilian Hoffmann & Jörg Henninger & Johannes Veith & Lars Richter & Benjamin Judkewitz, 2023. "Blazed oblique plane microscopy reveals scale-invariant inference of brain-wide population activity," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
    9. Frederic Fiore & Khaleel Alhalaseh & Ram R. Dereddi & Felipe Bodaleo Torres & Ilknur Çoban & Ali Harb & Amit Agarwal, 2023. "Norepinephrine regulates calcium signals and fate of oligodendrocyte precursor cells in the mouse cerebral cortex," Nature Communications, Nature, vol. 14(1), pages 1-25, December.
    10. Natalia V. Barykina & Erin M. Carey & Olena S. Oliinyk & Axel Nimmerjahn & Vladislav V. Verkhusha, 2024. "Destabilized near-infrared fluorescent nanobodies enable background-free targeting of GFP-based biosensors for imaging and manipulation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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