A biological light sheet links cellular voltage to mesoscopic brain dynamics

Abstract

Membrane voltage is the fundamental currency of neural computation, yet cellular-resolution voltage imaging of large neuronal populations in vivo remains limited by trade-offs among imaging speed, field of view, and optical sectioning. We overcome this challenge by encoding a biological light sheet in the brain: Selective Plane Expression (SPress) restricts fluorescent indicator expression to a user-defined, 20-m-thick plane, suppressing background at its source. Following one-time two-photon photoactivation, SPress enables standard widefield microscopes to capture high-contrast kilohertz voltage dynamics from hundreds of densely labeled neurons across millimeter-scale cortical sheets and columns in vivo. These recordings reveal mesoscopic subthreshold waves that flexibly reorganize population-wide spike timing, together with cellularscale wavefront microstructure that preserves stereotyped local recruitment biases. By shifting optical sectioning from instrumentation to gene expression, SPress makes kilohertz cellular resolution voltage imaging accessible across mesoscopic scales.