University of California, Berkeley, investigators have now built a high-speed camera to catch electrical and chemical signals in our brain: 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.
"This is really exciting, because we are now able to do something that people really weren't able to do before," said lead researcher Na Ji, a UC Berkeley associate professor of physics and of molecular and cell biology.
Using a wide-field 'mesoscope,' UC Berkeley researchers were able to image neurons (green) in a large chunk of the cortex of the brain of a living mouse. The area shows neurites in a volume 4.2 mm × 4.2 mm × 100 microns. The dark branches are blood vessels.
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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 is fast enough to trace electrical signals flowing through brain circuits.
With this technique, neuroscientists like Ji 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 do not 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.
"In diseases, many things are happening, even before you can see neurons firing, like all the subthreshold events," said Ji, a member of UC Berkeley's Helen Wills Neuroscience Institute. "We have never looked at how a disease will change with subthreshold input. Now, we have a handle to address that."
Ji and her colleagues reported the new imaging technique in Nature Methods. In the same issue, she and other colleagues also published a paper demonstrating a different technique for imaging calcium signaling over much of an entire hemisphere of the mouse brain at once, one that uses a wide-field-of-view "mesoscope" with two-photon imaging and Bessel focus scanning. Calcium concentrations are linked with voltage changes as signals are transmitted through the brain.
"This is the first time anyone has shown in three dimensions the neural activity of such a large volume of the brain at once, which is far beyond what electrodes can do," Ji said. "Furthermore, our imaging approach gives us the ability to resolve the synapses of each neuron."
MEDICA-tradefair.com; Source: University of California – Berkeley