Extended field-of-view ultrathin microendoscopes for high-resolution two-photon imaging with minimal invasiveness

• Published in: eLife Vol. 9
• Main Authors: Antonini, Andrea, Sattin, Andrea, Moroni, Monica, Bovetti, Serena, Moretti, Claudio, Succol, Francesca, Forli, Angelo, Vecchia, Dania, Rajamanickam, Vijayakumar P, Bertoncini, Andrea, Panzeri, Stefano, Liberale, Carlo, Fellin, Tommaso
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 13.10.2020; eLife Sciences Publications, Ltd; eLife Sciences Publications Ltd
• Subjects: 3D microprinting; Aberration correction; Animals; Behavior, Animal; Endoscopes; Female; Male; Mice; Mice, Inbred C57BL; microendoscopes; Microscopy, Fluorescence, Multiphoton - instrumentation; Microscopy, Fluorescence, Multiphoton - methods; network dynamics; Neurons - physiology; Neuroscience; Neurosciences; thalamus; Thalamus - diagnostic imaging; Thalamus - physiology; Tools and Resources; two-photon imaging; mouse; two-photon imaging; microendoscopes; neuroscience; Aberration correction; network dynamics; 3D microprinting; thalamus
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.58882

Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin (≤500 µm) microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV ( eFOV ) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV -microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV- microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV- microendoscopes are, therefore, small-cross-section ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution.