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Cellular-resolution three-photon ultra-deep imaging (TrUDI) of neuronal population activity at 2-mm depth in the mammalian brain.
Nature Methods · · Journal Article
Santra, Barber + more
Abstract ↗AI summary
The abstract is read at the publisher; the summary is JClub's.
TrUDI enables in vivo cellular-resolution recordings of neuronal population activity at tissue depths up to ~2 mm in mouse cortex and hippocampus, with a ~250-fold increase in detected fluorescence photon yield.
- Why it matters: Multiphoton imaging of neuronal population activity in the scattering mammalian brain is limited by an “exponentially hard” depth problem, where out-of-focus background can exceed in-focus signal.
- What they did: The authors optimized in-focus fluorescence signal in a three-photon ultra-deep imaging (TrUDI) system by matching excitation laser, optics, and acquisition to linear and nonlinear limits for safe exposure while meeting single-cell Ca2+ imaging requirements.
- The result: TrUDI achieves ~250-fold higher photon yield at the same laser power as previous approaches, enabling ~230×230 µm² fields of view at 8.6 Hz for recordings up to ~2 mm.
The findingWhy it mattersWhat they didThe result