Measuring neuronal input-output operations in vivo with random access projection microscopy

SLAP2, a two-photon random access projection microscope in behaving mice, enables submicron synapse imaging at ~200 Hz for hundreds of sites and 2–10 kHz dendritic voltage.

• Why it matters: Neuronal computation depends on how many synapses integrate into millisecond spiking outputs, but existing in vivo imaging struggles to capture many subcellular inputs fast enough.
• What they did: The authors built SLAP2 with random access and real-time hardware motion correction, using flexible scanning to measure hundreds of synapses at ~200 Hz, >800 synapses at 50–100 Hz, and dendritic voltage at 2–10 kHz.
• The result: In visual cortex pyramidal neurons, simultaneous dendritic glutamate and somatic calcium imaging shows nonlinear input-output amplification for stimulus onset and preferred orientation, linked to spatially organized inputs and stronger trial-to-trial coupling.

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