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Fast optical recording of neuronal activity by three-dimensional custom-access serial holography

W Akemann, S Wolf, V Villette, B Mathieu, A Tangara, J Fodor, C Ventalon, J-F Léger, S Dieudonné, L Bourdieu


Optical recording of neuronal activity in three-dimensional (3D) brain circuits at cellular and millisecond resolution in vivo is essential for probing information flow in the brain. While random-access multiphoton microscopy permits fast optical access to neuronal targets in three dimensions, the method is challenged by motion artifacts when recording from behaving animals. Therefore, we developed three-dimensional custom-access serial holography (3D-CASH). Built on a fast acousto-optic light modulator, 3D-CASH performs serial sampling at 40 kHz from neurons at freely selectable 3D locations. Motion artifacts are eliminated by targeting each neuron with a size-optimized pattern of excitation light covering the cell body and its anticipated displacement field. Spike rates inferred from GCaMP6f recordings in visual cortex of awake mice tracked the phase of a moving bar stimulus with higher spike correlation between intra compared to interlaminar neuron pairs. 3D-CASH offers access to the millisecond correlation structure of in vivo neuronal activity in 3D microcircuits.
© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.

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Nat Methods. 2022 Jan ;19(1):100-110. doi : 10.1038/s41592-021-01329-7