Measuring neuronal input-output operations in vivo with random access projection microscopy
Year: 2026
Type: preprint
Abstract: Neurons transform thousands of synaptic inputs into spiking output, and understanding this transformation requires measuring many submicron synapses at millisecond timescales in vivo. Here we present SLAP2, a two-photon random access projection microscope with no per-target access time cost, yielding over 5-fold faster imaging than existing methods, and performant real-time hardware motion correction. Flexible scanning modes enable measurement of hundreds of synapses at ~200 Hz, >800 synapses volumetrically at 50-100 Hz, and compartment-resolved dendritic voltage at 2-10 kHz in behaving mice. Simultaneous dendritic glutamate and somatic calcium imaging in visual cortex pyramidal neurons revealed nonlinear input-output amplification of stimulus onset and preferred stimulus orientation responses. Amplified features are associated with spatially organized inputs and stronger trial-to-trial coupling between synaptic activity and somatic output. These measurements establish SLAP2 as a powerful tool for recording intricate patterns of subcellular fluorescence dynamics in behaving animals.
Authors: Michael E. Xie, Maedeh Seyedolmohadesin, Manni He, Lillian Li, Yukun Alex Hao, Daniel Flickinger, Ryan Gibiser, Jonathan King, Kort Driessen, Jimin Park, R Carter Peene, Henry Loeffler, Katrina Nguyen, Madeline Tom, Ali Williford, Jackie Swapp, Giulio Tononi, Chiara Cirelli, Michael Z. Lin, Jerome Lecoq, Bruce E. Kimmel, Jack Glaser, Matthew D. Golub, Adam S. Charles, Karel Svoboda, Georg Jaindl, Kaspar Podgorski
Language: English
Subfield: Biophysics
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7225383963