overview: Researchers have developed a new sensor that allows scientists to image the brain deeper into the brain than current technology allows, without missing a signal for long periods of time.
sauce: Baylor College of Medicine
While reading these words, specific areas of the brain show electrical activity in milliseconds. Visualizing and measuring this electrical activity is important for understanding how the brain can see, move, act and read these words.
However, technical limitations are holding back neuroscientists from reaching their goal of better understanding how the brain works.
Scientists from Baylor College of Medicine and Collaborating Institutions Report in Journal cell A new sensor that allows neuroscientists to image brain activity without loss of signal, for longer and deeper into the brain than was previously possible.
The study paves the way for new discoveries about how the brains of awake and active animals work, both in healthy animals and in animals with neurological disorders.
The Holy Grail of Neuroscience
“Not only is electrical activity in the brain very fast, but it also involves different cell types with different roles in brain computation,” says McNair, corresponding author and assistant professor of neuroscience at Baylor. Academician Dr. Francois St-Pierre said: He is also Adjunct Assistant Professor of Electrical and Computer Science at Rice University.
“It has been difficult to understand how to noninvasively observe the millisecond electrical activity of individual neurons in specific cell types in animals undergoing activity. It was the holy grail of imaging.”
There are existing techniques for measuring electrical activity in the brain. “For example, electrodes can record very fast activity, but they can’t tell what type of cell they’re listening to,” he said.
Researchers also use fluorescent proteins that respond to changes in calcium associated with electrical activity. These changes in fluorescence can be tracked using two-photon microscopy.
“These kinds of sensors are great at determining which neurons are active and which are not. , many important signals are lost.”
The goal of St-Pierre and his colleagues was to combine the best of these methodologies, developing sensors that could monitor the activity of specific cell types while capturing high-speed brain signals. “We have achieved this with a new generation of artificial fluorescent proteins called genetically encoded voltage indicators or GEVIs,” said St-Pierre.
Co-first authors Zhuohe (Harry) Liu, Xiaoyu (Helen) Lu, and Yueyang (Eric) Gou provide a better and more efficient way to design and optimize fluorescent voltage indicators for two-photon microscopy. Created and used an automated system. It is the standard method for non-invasive deep tissue imaging in neuroscience.
“Using this system, we tested thousands of indicator variants and identified JEDI-2P, which is faster, brighter, more sensitive and photostable than its predecessor. ‘ said a graduate student in electrical and computer engineering at Rice in the St-Pierre lab.
“Using JEDI-2P, we solved three key drawbacks of previous methods,” said a graduate student in the Systems, Synthetic and Physical Biology (SSPB) program at Rice University, working at the St. Pierre Institute. said Mr. Lu.
“First, it will allow us to track the electrical activity of living animals for as long as 40 minutes instead of minutes at most. Third, the indicators are bright and produce a large signal in response to brain activity, allowing us to image individual cells deep within the brain.”
Until now, researchers have been limited to looking at the surface of the brain, but “most brain activity is clearly not confined to the first 50 microns of the brain surface,” says St- says Pierre. “Our methodology allows researchers to non-invasively monitor voltage signals deep in the cortex for the first time,” said Gou, a former member of the St-Pierre lab now at Baylor’s Graduate Program in Neuroscience. said.
Baylor co-authors Andreas Tolias, Ph.D., Professor of Neuroscience, and Dr. Jacob Reimer, Ph.D., Assistant Professor of Neuroscience, found that JEDI-2P captured electrical activity in mice using imaging equipment available in many neuroimaging labs. I have proven that I can report.
Co-author Stéphane Dieudonné (École Normale Supérieure, France) showed deep and ultrafast detection of electrical signals in the mouse brain by monitoring JEDI-2P fluorescence with a rapid microscopy method called ULoVE .
Co-author’s laboratory. Katrin Franke (group her leader, University of Tübingen, Germany) and Tom Clandinin (Stanford University) showed how to apply JEDI-2P to image electrical activity in retinas and flies, respectively.
Taken together, this international collaboration has demonstrated that new techniques can be readily deployed by neuroscience groups working on different animal models and using different microscopy techniques.
“In 2014, I gave a presentation at a neuroscience conference about the first version of this indicator and people were wide-eyed. Because of this, we thought that rapid voltage imaging using fluorescent indicators would never be possible in awake animals. , there is still room for the indicator to evolve — it won’t be the last JEDI!”
About this Neurotech Research News
author: press office
sauce: Baylor College of Medicine
contact: Press Office – Baylor College of Medicine
image: image is public domain
Original research: open access.
Zhuohe Liu et al cell
Sustained deep-tissue voltage recordings using advanced high-speed indicators for two-photon microscopy
- JEDI-2P is a faster, brighter, more sensitive and photostable voltage indicator.
- JEDI-2P was designed using a two-photon multiparameter screening platform
- JEDI-2P enabled two-photon voltage recordings in retinal explants, flies, and mice
- JEDI-2P generated deep (cortical layer 5) and long (>40 min) recordings in mice
Genetically encoded voltage indicators are a novel tool for monitoring voltage dynamics with cell-type specificity. However, current indicators enable a narrow range of applications due to their poor performance under two-photon microscopy, a method of choice for deep tissue recording.
To improve the indicator, we developed a multiparameter high-throughput platform to optimize the voltage indicator for two-photon microscopy. Using this system, we identified JEDI-2P. It is a faster, brighter, more sensitive and more photostable indicator than its predecessor.
We demonstrate that JEDI-2P can report light-evoked responses at axon terminals. Drosophila Interneurons and dendrites and cell bodies of isolated mouse retinal amacrine cells. JEDI-2P is also capable of optically recording voltage dynamics of individual cortical neurons in mice that are awake for more than 30 min using both resonance scanning and ULoVE random access microscopy.
Finally, JEDI-2P ULoVE recordings can reliably detect spikes at depths greater than 400 μm and report voltage correlations in pairs of neurons.