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

Antonini, A.; Sattin, A.; Moroni, M.; Bovetti, S.; Moretti, C.; Succol, F.; Forli, A.; Vecchia, D.; Rajamanickam, V. P.; Bertoncini, A.; Panzeri, S.; Liberale, C.; Fellin, T.

doi:10.1101/2020.05.14.095299

bioRxiv · 10.1101/2020.05.14.095299

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

Antonini, A.·Sattin, A.·Moroni, M.·Bovetti, S.·Moretti, C.·Succol, F.·Forli, A.·Vecchia, D.·Rajamanickam, V. P.·Bertoncini, A.·Panzeri, S.·Liberale, C.·Fellin, T.

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Abstract

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 {micro}m) 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.

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Antonini, A., Sattin, A., Moroni, M., Bovetti, S., Moretti, C., Succol, F., Forli, A., Vecchia, D., Rajamanickam, V. P., Bertoncini, A., Panzeri, S., Liberale, C., Fellin, T.. 2020-05-14. Extended field-of-view ultrathin microendoscopes for high-resolution two-photon imaging with minimal invasiveness in awake mice. https://doi.org/10.1101/2020.05.14.095299

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