Zebrafish have been a good model organism due to their similar genetic structure to humans. In a recent discovery, researchers from Cornell University captured images of an intact zebrafish brain using a microscopy method called deep three-photon imaging.
The study was published in the journal Nature Methods, describing a new brain imaging technique capturing all stages of development of the zebrafish. The researchers believe the results can help study brain disorders in humans such as neurological diseases or autism.
Live imaging while the zebrafish are still young was done easily since they are translucent at that age. However, they turn opaque as they turn into an adult, making it difficult for researchers to see the brain at later stages of development.
Microscopic Laser Imaging
Alongside Cornell Neurotech, the team developed a new microscopy tool with calcium sensors. The sensors indicate which specific neurons are active.
Professor Joseph Fetcho from Cornell Neurotech explained that essentially, all vertebrate brains are the same. Almost all brain regions are similar in all vertebrates since all species "have to do the same things to survive and reproduce."
When neurons (nerve cells) are activated, they are filled with calcium. The zebrafish from Fetcho's studies were genetically engineered with a protein that binds to calcium within neurons.
The protein also lights up when triggered by a 480-nanometer wavelength laser light, enabling scientists to capture images of the fluorescing cells. However, at this wavelength, other fluorescent proteins are also activated along the beam, causing imaging to blur.
The new technique uses 1,400 nm wavelength photons to target regions of the brain more accurately. As a result, three photons at different depths can create better three-dimensional imaging of the entire adult zebrafish brain.
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Implications for Human Brain Conditions
Dr. David Sinefeld explained that uses very short pulses of lasers interact with brain molecules in a certain way that isn't hindered by layers of tissue. Even the neurons deep inside the brain can be captured with very high resolution.
"This could be a game-changer in the field of neuroscience," he said, hoping that he can establish the methods at the Jerusalem College of Technology where he teaches. Examining the brain has been "a problem that everyone dreams of solving," said Dr. Sinefeld.
In the study, the authors noted that "behaviors emerge from activity throughout the brain." The researchers can then use the method on zebrafish that are genetically engineered to develop versions of brain disorders such as autism and track its progress during the entire life of the fish.
Later on, treatments can be developed to improve the brain functions of fish with neurological problems. Scientists could also keep track of how brain structure and function alter as a neurological condition improves. Fetcho said that their research is a step closer to curing some of the worst brain disorders that people suffer from while keeping track of how people respond to treatment and progress with their illness.
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