Considering That the 1950 s at least, researchers have actually hypothesized that the brain is a type of computer system in which neurons make up intricate circuits that carry out unknown numbers of calculations every second. Decades later on, neuroscientists know that these brain circuits exist, yet technical limitations have actually kept most details of their computations out of reach.
Now, neuroscientists reported December 12 in Cell, they may lastly be able to expose what circuits deep in the brain depend on, thanks in big part to a particle that illuminate brighter than ever before in reaction to subtle electrical modifications that nerve cells use to perform their calculations.
Presently, among the best ways to track nerve cells’ electrical activity is with molecules that illuminate in the presence of calcium ions, a proxy for a neuron spike, the moment when one neuron passes an electrical signal to another. But calcium flows too slowly to capture all the information of a nerve cell spike, and it doesn’t respond at all to the subtle electrical changes that lead up to a spike. (One alternative is to implant electrodes, however those implants ultimately damage nerve cells, and it isn’t practical to put electrodes in more than a handful of neurons simultaneously in living animals.)
To fix those issues, scientists led by Michael Lin, an associate professor of neurobiology and of bioengineering and a member of the Wu Tsai Neurosciences Institute, and Stéphane Dieudonné, an INSERM research director at the École Normale Supérieure in Paris, concentrated on fluorescent molecules whose brightness reacts directly to voltage modifications in neurons, an idea Lin and his team had been dealing with for several years.
Still, those particles had an issue of their own: Their brightness hasn’t always been that responsive to voltage, so Lin and his group at Stanford turned to a well-known method in biology called electroporation.
Dieudonné and his lab focused on another issue: how to scan neurons deep in the brain more efficiently. To make fluorescent molecules such as ASAP3 illuminate deep in the brain, scientists frequently utilize a method called two-photon imaging, which employs infrared laser beams that can permeate through tissue. Then, in order to scan multiple neurons fast enough to see a spike, which itself lasts only about a thousandth of a second, researchers should move the laser area rapidly from neuron to nerve cell– something hard to do reliably in moving animals. The solution, Dieudonné and coworkers discovered, was a brand-new algorithm called ultrafast regional volume excitation, or ULoVE, in which a laser rapidly scans numerous points in the volume around a neuron, all at once.
Such strategies, where each laser pulse is shaped and sent out to the best volume within the tissue, make up the optimal usage of light power and will hopefully permit us to record and promote millions of areas in the brain each second.”
Stéphane Dieudonné, INSERM research director at the École Normale Supérieure in Paris
Putting those techniques together, the researchers displayed in mice that they could track fine information of brain activity in much of the mouse cortex, the leading layers of the brain that control movement, decision making and other greater cognitive functions.
” You can now look at nerve cells in living mouse brains with very high precision, and you can track that for long periods of time,” Lin stated. To name a few things, that opens the door to studying not only how nerve cells process signals from other nerve cells and how they decide, so to speak, when to increase, but also how nerve cells’ estimations alter in time.
In the meantime, Lin and colleagues are concentrated on further improving on their techniques. “ASAP3 is extremely usable now, but we’re confident there will be an ASAP4 and ASAP5,” he stated.
Villette, V., et al.(2019) Ultrafast Two-Photon Imaging of a High-Gain Voltage Indication in Awake Behaving Mice. Cell