Prolonged Single Neuron Voltage Imaging in Behaving Mammals

Long-term recording of single-neuron membrane voltage dynamics during behavior is highly desirable. Using ElectraOFF, a fully genetically encoded, photostable, high-performance fluorescence voltage indicator, we achieve routine cellular-resolution imaging over tens of minutes, occasionally up to eighty minutes, in behaving mice with minimal signal loss across neuron types and brain regions. This extended recording capability reveals plasticity changes throughout intracranial electrical neuromodulation, highlighting the novel insights enabled by prolonged voltage imaging.