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110 μm thin endo-microscope for deep-brain in vivo observations of neuronal connectivity, activity and blood flow dynamics

Author

Listed:
  • Miroslav Stibůrek

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Petra Ondráčková

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Tereza Tučková

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Sergey Turtaev

    (Leibniz Institute of Photonic Technology)

  • Martin Šiler

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Tomáš Pikálek

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Petr Jákl

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • André Gomes

    (Leibniz Institute of Photonic Technology)

  • Jana Krejčí

    (Institute of Biophysics of the Czech Academy of Sciences)

  • Petra Kolbábková

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Hana Uhlířová

    (Institute of Scientific Instruments of the Czech Academy of Sciences)

  • Tomáš Čižmár

    (Institute of Scientific Instruments of the Czech Academy of Sciences
    Leibniz Institute of Photonic Technology
    Friedrich Schiller University Jena)

Abstract

Light-based in-vivo brain imaging relies on light transport over large distances of highly scattering tissues. Scattering gradually reduces imaging contrast and resolution, making it difficult to reach structures at greater depths even with the use of multiphoton techniques. To reach deeper, minimally invasive endo-microscopy techniques have been established. These most commonly exploit graded-index rod lenses and enable a variety of modalities in head-fixed and freely moving animals. A recently proposed alternative is the use of holographic control of light transport through multimode optical fibres promising much less traumatic application and superior imaging performance. We present a 110 μm thin laser-scanning endo-microscope based on this prospect, enabling in-vivo volumetric imaging throughout the whole depth of the mouse brain. The instrument is equipped with multi-wavelength detection and three-dimensional random access options, and it performs at lateral resolution below 1 μm. We showcase various modes of its application through the observations of fluorescently labelled neurones, their processes and blood vessels. Finally, we demonstrate how to exploit the instrument to monitor calcium signalling of neurones and to measure blood flow velocity in individual vessels at high speeds.

Suggested Citation

  • Miroslav Stibůrek & Petra Ondráčková & Tereza Tučková & Sergey Turtaev & Martin Šiler & Tomáš Pikálek & Petr Jákl & André Gomes & Jana Krejčí & Petra Kolbábková & Hana Uhlířová & Tomáš Čižmár, 2023. "110 μm thin endo-microscope for deep-brain in vivo observations of neuronal connectivity, activity and blood flow dynamics," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36889-z
    DOI: 10.1038/s41467-023-36889-z
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    References listed on IDEAS

    as
    1. Tomáš Čižmár & Kishan Dholakia, 2012. "Exploiting multimode waveguides for pure fibre-based imaging," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
    2. Sanja Mikulovic & Carlos Ernesto Restrepo & Samer Siwani & Pavol Bauer & Stefano Pupe & Adriano B. L. Tort & Klas Kullander & Richardson N. Leão, 2018. "Ventral hippocampal OLM cells control type 2 theta oscillations and response to predator odor," Nature Communications, Nature, vol. 9(1), pages 1-15, December.
    3. Murat Yildirim & Hiroki Sugihara & Peter T. C. So & Mriganka Sur, 2019. "Functional imaging of visual cortical layers and subplate in awake mice with optimized three-photon microscopy," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    4. Shuhui Li & Simon A. R. Horsley & Tomáš Tyc & Tomáš Čižmár & David B. Phillips, 2021. "Memory effect assisted imaging through multimode optical fibres," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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