Cortex-wide imaging in naturally behaving mice with 1-gram wireless mesoscopes

Revealing how distributed cortical circuits coordinate behavior in freely moving animals remains a central challenge in systems neuroscience, constrained by limited fields of view, low throughput, and the tethering required by current miniaturized microscopes^1-4. Here, we present Airscope, a wireless mesoscope delivering 4 μm lateral resolution across a 6 mm field of view at 12.5 Hz, weighing 1.0 gram. An aspheric-lens design achieves a 2.84× shorter total track length than previous miniaturized microscopes^1,2,5,6 while matching the neuron yield of benchtop one-photon mesoscopes; a tailored wireless link supports cable-free calcium imaging from >8,500 neurons per animal (25‑fold increase). Paired with a zero-shot behavior analyzer, Airscope enables cortical imaging across rich behavioral conditions, including room-scale enriched arenas, swimming assays, and multi-organ implantation, with concurrent recording from multiple animals. Using Airscope, we demonstrate versatile applications of untethered cortical imaging across diverse behavioral paradigms. We identify cortical activity patterns across multiple dorsal regions that correlate with behavioral signatures of social dominance, and show dorsal-cortical population activity prospectively decodes competition outcomes across paired animals. We observe reward-location-associated cortical activity patterns during maze exploration, and characterize Granger-causal influence from spinal cord to cortex during fear conditioning, enabled by simultaneous brain-spinal recordings. By uniting large-scale, cellular-resolution recording with unconstrained behavior, Airscope makes naturalistic, multi-animal cortical recording experimentally practical, and provides a broadly accessible technology for systems neuroscience.