On Mar. 19, 2020, University of California, Berkeley, investigators have now built such a camera: a microscope that can image the brain of an alert mouse 1,000 times a second, recording for the first time the passage of millisecond electrical pulses through neurons.

The new imaging technique combines two-photon fluorescence microscopy and all-optical laser scanning in a state-of-the-art microscope that can image a two-dimensional slice through the neocortex of the mouse brain up to 3,000 times per second. That’s fast enough to trace electrical signals flowing through brain circuits.

With this technique, neuroscientists can now clock electrical signals as they propagate through the brain and ultimately look for transmission problems associated with disease.

One key advantage of the technique is that it will allow neuroscientists to track the hundreds to tens of thousands of inputs any given brain cell receives from other brain cells, including those that don’t trigger the cell to fire. These sub-threshold inputs — either exciting or inhibiting the neuron — gradually add up to a crescendo that triggers the cell to fire an action potential, passing information along to other neurons.

The typical method for recording electrical firing in the brain, via electrodes embedded in the tissue, detects only blips from a few neurons as the millisecond voltage changes pass by. The new technique can pinpoint the actual firing neuron and follow the path of the signal, millisecond by millisecond.