Imaging sensory transmission and neuronal plasticity in primary sensory neurons with a positively tuned voltage...

Primary sensory neurons convert external stimuli into electrical signals, yet how heterogeneous neurons encode distinct sensations remains unclear. In vivo dorsal root ganglia (DRG) imaging with genetically-encoded Ca²⁺ indicators (GECIs) enables mapping of neuronal activity from over 1800 neurons per DRG in live mice, offering high spatial and populational resolution. However, GECIs' slow Ca²⁺ response kinetics limit the temporal accuracy of neuronal electrical dynamics. Genetically-encoded voltage indicators (GEVIs) provide real-time voltage tracking but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4.4-Kv, a bright and fast positively tuned GEVI, to dissect temporal dynamics of DRG neuron responses to mechanical, thermal, or chemical stimulation in live male and female mice. ASAP4.4-Kv revealed previously unrecognized cell-to-cell electrical synchronization and robust dynamic transformations in sensory coding following tissue injury. Combining GEVI and GECI imaging empowers spatiotemporal analysis of sensory signal processing and integration mechanisms in vivo.