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Neuroscience

Deep brain imaging on the move

Nature Methods (2023)Cite this article

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New three-photon miniature microscopes open the study of neuronal networks to those deep in the brains of behaving animals.

For imaging deep brain regions, miniaturized multiphoton microscopes offer several advantages over their 1P counterparts, such as an improved optical sectioning and reduced background contamination. The resilience to light scattering at higher imaging depth can be explained by vascular and neuronal brain tissues having vastly different light absorption and scattering properties in the visible, far-red, and infrared wavelengths17. Second, in contrast to 1P imaging, which is dominated by background fluorescence excitation, the nonlinear absorption properties of multiphoton microscopy substantially reduce out-of-plane excitation. Two-photon microscopy suffers from this contamination at higher imaging depths and laser intensities, whereas 3P imaging greatly eliminates this residual out-of-plane excitation18.

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Fig. 1: Single-photon and multiphoton miniature microscopy in freely behaving animals.

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Acknowledgements

This work was supported by the Swiss National Science Foundation (B.F.G., CRSII5-173721 and 315230189251), ETH project funding (B.F.G., ETH-20 19-01), the Human Frontiers Science Program (RGY0072/2019) and funding from the Dr. Wilhelm Hurka Foundation Zurich. We further thank A. Hoffmann for discussions and for helping to acquire the 1P FOV images.

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Authors and Affiliations

  1. Mindscope program, Allen Institute, Seattle, WA, USA

    Jérôme A. Lecoq

  2. Institute of Neuroinformatics, University of Zurich and ETH Zurich, Zurich, Switzerland

    Roman Boehringer & Benjamin F. Grewe

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  1. Jérôme A. Lecoq
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  2. Roman Boehringer
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  3. Benjamin F. Grewe
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Correspondence to Jérôme A. Lecoq or Benjamin F. Grewe.

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Lecoq, J.A., Boehringer, R. & Grewe, B.F. Deep brain imaging on the move. Nat Methods (2023). https://doi.org/10.1038/s41592-023-01808-z

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