Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators

Lin Tian, S. Andrew Hires, Tianyi Mao, Daniel Huber, M. Eugenia Chiappe, Sreekanth H. Chalasani, Leopoldo Petreanu, Jasper Akerboom, Sean A. McKinney, Eric R. Schreiter, Cornelia I. Bargmann, Vivek Jayaraman, Karel Svoboda, Loren L. Looger

Research output: Contribution to journalArticle

1216 Scopus citations

Abstract

Genetically encoded calcium indicators (GECIs) can be used to image activity in defined neuronal populations. However, current GECIs produce inferior signals compared to synthetic indicators and recording electrodes, precluding detection of low firing rates. We developed a single-wavelength GCaMP2-based GECI (GCaMP3), with increased baseline fluorescence (3-fold), increased dynamic range (3-fold) and higher affinity for calcium (1.3-fold). We detected GCaMP3 fluorescence changes triggered by single action potentials in pyramidal cell dendrites, with signal-to-noise ratio and photostability substantially better than those of GCaMP2, D3cpVenus and TN-XXL. In Caenorhabditis elegans chemosensory neurons and the Drosophila melanogaster antennal lobe, sensory stimulation-evoked fluorescence responses were significantly enhanced with GCaMP3 (4-6-fold). In somatosensory and motor cortical neurons in the intact mouse, GCaMP3 detected calcium transients with amplitudes linearly dependent on action potential number. Long-term imaging in the motor cortex of behaving mice revealed large fluorescence changes in imaged neurons over months.

Original languageEnglish (US)
Pages (from-to)875-881
Number of pages7
JournalNature Methods
Volume6
Issue number12
DOIs
StatePublished - Nov 9 2009

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Tian, L., Hires, S. A., Mao, T., Huber, D., Chiappe, M. E., Chalasani, S. H., Petreanu, L., Akerboom, J., McKinney, S. A., Schreiter, E. R., Bargmann, C. I., Jayaraman, V., Svoboda, K., & Looger, L. L. (2009). Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators. Nature Methods, 6(12), 875-881. https://doi.org/10.1038/nmeth.1398