Title: From Spikes To Waves: Multiscale, Cell-Type-Specific Voltage Imaging For Decoding How Brains Compute.

Abstract: How do distributed neural circuits compute to support perception, memory, and decision-making? For decades, systems neuroscience has primarily focused on discrete spikes as the unit of computation. Yet spikes are sparse readouts of a richer dynamical process that unfolds continuously in membrane voltage across cell types, space, and time. A mechanistic understanding of how brains compute requires direct access to cross-scale voltage dynamics of defined circuit elements and their real-time interaction.

In this talk, I will describe three high-speed voltage imaging techniques that enable optical measurement of membrane voltage in genetically identified and projection-targeted neurons of awake, behaving mice. Together, these approaches bridge scales: from single-cell subthreshold fluctuations and action potentials to large-scale, cell-type-specific network dynamics. First, I will present a microscopy technique that visualizes both spikes and subthreshold activity from ~100 individual neurons, comprising up to four neuron-classes simultaneously. Second, I will describe an ultrasensitive fiber photometry device that tracks high-frequency membrane oscillations within a specific neuron type population in freely moving animals. Lastly, to study the spatiotemporal properties of these oscillations, I will introduce a wide-field mesoscopic imaging approach that resolves fast, high-frequency waves propagating across millimeter-scale neural circuits. Using these tools, I have uncovered previously undocumented forms of distributed voltage dynamics that differ across cell types, frequency bands, and brain states. These findings suggest that neural computation may rely not only on discrete spikes but also on spatially structured voltage dynamics that coordinate distributed circuits.

Overall, voltage imaging directly visualizes the rich repertoire of cross-scale neural dynamics that shape circuit function, providing a tractable path toward decoding how computation unfolds in healthy and dysfunctional brains.