Our brain contains tens of billions of nerve cells (neurons) which constantly communicate
with each other by sending chemical and electrical flashes, each lasting a short one millisecond.
In every millisecond, these billions of swift-flying flashes altogether traveling in a giant star-map
in the brain that lights up a tortuous glittering pattern.
They are the origins of all body functions and behaviours such as emotions, perceptions,
thoughts, actions, and memories; and also brain diseases e.g. alzheimer's and parkinson's
diseases, in case of abnormalities.
One grand challenge for neuroscience in the 21st century is to capture these complex flickering
patterns of neural activities, which is the key to an integrated understanding of the
large-scale brain-wide interactions.
To capture these swift-flying signals live has been a challenge to neuroscientists and
biomedical engineers.
It would take a high-speed microscope into the brain, which has not been possible so
far.
A research team from University of Hong Kong (HKU) and UC Berkeley offers a novel solution
with their super high-speed microscope - two-photon fluorescence microscope, which has successfully
recorded the millisecond electrical signals in the neurons of an alert mouse.
The new technique is minimally invasive to the animal being tested compared to the traditional
method that require inserting an electrode into the brain tissue.
Not only is this less damaging to the neurons but also can pinpoint individual neurons and
trace their firing paths, millisecond by millisecond.
The result of this ground-breaking work has recently been published in the academic journal
Nature Methods.
At the heart of the high-speed microscope is an innovative technique called FACED (free-space
angular-chirp-enhanced delay imaging).
FACED makes use of a pair of parallel mirrors which generate a shower of laser pulses to
create a super-fast sweeping laser beam at least 1,000 times faster than the existing
laser-scanning methods.
In the experiment, the microscope projected a beam of sweeping laser over the mouse's
brain and captured 1,000 to 3,000 full 2D scans of a single mouse brain layer every
second.
To probe the genuine electrical signals that pulse between the neurons, the team inserted
a biosensor (protein molecules) into the neurons of the mouse brain.
These engineered proteins will light up (or fluoresce) whenever there is a voltage signal
passes through the neurons.
The emitted light is then detected by the microscope and formed into a 2D image that
visualises the locations of these voltage changes.
Apart from electrical signals, the team also used the microscope to capture the slow-motion
of chemical signals in the mouse brain, such as calcium and glutamate, a neurotransmitter,
as deep as one-third of a millimeter from the brain's surface.
A notable advantage of this technique is the ability to track the signals that do not trigger
the neuron to fire - weak neuronal signals (called sub-threshold signals) that are often
difficult to capture and detect, which could also happen in many disease condition in the
brain, but have yet been studied in detail because of the lack of high-speed technique
like the one developed by the team.
Another important feature of the novel technique is that it is minimally invasive.
The classical method for recording electrical firing in the brain is to physically embed
or implant electrodes in the brain tissue.
However, such physical intrusion could cause damage to the neurons, and can only detect
fuzzy signals from a couple of neurons.