Mesoscale Imaging System
Posted on by Dr. Francis Collins
There’s so much to celebrate about our country this Fourth of July. That includes giving thanks to all those healthcare providers who have put themselves in harm’s way to staff the ERs, hospital wards, and ICUs to care for those afflicted with COVID-19, and also for everyone who worked so diligently to develop, test, and distribute COVID-19 vaccines.
These “shots of hope,” created with rigorous science and in record time, are making it possible for a great many Americans to gather safely once again with family and friends. So, if you’re vaccinated (and I really hope you are—because these vaccines have been proven safe and highly effective), fire up the grill, crank up the music, and get ready to show your true red, white, and blue colors. My wife and I—both fully vaccinated—intend to do just that!
To help get the celebration rolling, I’d like to share a couple minutes of some pretty amazing biological fireworks. While the track of a John Philip Sousa march is added just for fun, what you see in the video above is the result of some very serious neuroscience research that is scientifically, as well as visually, breath taking. Credit for this work goes to an NIH-supported team that includes Ricardo Azevedo and Sunil Gandhi, at the Center for the Neurobiology of Learning and Memory, University of California, Irvine, and their collaborator Damian Wheeler, Translucence Biosystems, Irvine, CA. Azevedo is also an NIH National Research Service Award fellow and a Medical Scientist Training Program trainee with Gandhi.
The team’s video starts off with 3D, colorized renderings of a mouse brain at cellular resolution. About 25 seconds in, the video flashes to a bundle of nerve fibers called the fornix. Thanks to the wonders of fluorescent labeling combined with “tissue-clearing” and other innovative technologies, you can clearly see the round cell bodies of individual neurons, along with the long, arm-like axons that they use to send out signals and connect with other neurons to form signaling circuits. The human brain has nearly 100 trillion of these circuits and, when activated, they process incoming sensory information and provide outputs that lead to our thoughts, words, feelings, and actions.
As shown in the video, the nerve fibers of the fornix provide a major output pathway from the hippocampus, a region of the brain involved in memory. Next, we travel to the brain’s neocortex, the outermost part of the brain that’s responsible for complex behaviors, and then move on to explore an intricate structure called the corticospinal tract, which carries motor commands to the spinal cord. The final stop is the olfactory tubercle —towards the base of the frontal lobe—a key player in odor processing and motivated behaviors.
Azevedo and his colleagues imaged the brain in this video in about 40 minutes using their imaging platform called the Translucence Biosystems’ Mesoscale Imaging System™. This process starts with a tissue-clearing method that eliminates light-scattering lipids, leaving the mouse brain transparent. From there, advanced light-sheet microscopy makes thin optical sections of the tissue, and 3D data processing algorithms reconstruct the image to high resolution.
Using this platform, researchers can take brain-wide snapshots of neuronal activity linked to a specific behavior. They can also use it to trace neural circuits that span various regions of the brain, allowing them to form new hypotheses about the brain’s connectivity and how such connectivity contributes to memory and behavior.
The video that you see here is a special, extended version of the team’s first-place video from the NIH-supported BRAIN Initiative’s 2020 “Show Us Your BRAINS!” imaging contest. Because of the great potential of this next-generation technology, Translucence Biosystems has received Small Business Innovation Research grants from NIH’s National Institute of Mental Health to disseminate its “brain-clearing” imaging technology to the neuroscience community.
As more researchers try out this innovative approach, one can only imagine how much more data will be generated to enhance our understanding of how the brain functions in health and disease. That is what will be truly spectacular for everyone working on new and better ways to help people suffering from Alzheimer’s disease, Parkinson’s disease, schizophrenia, autism, epilepsy, traumatic brain injury, depression, and so many other neurological and psychiatric disorders.
Wishing all of you a happy and healthy July Fourth!
Medical Scientist Training Program (National Institute of General Medical Sciences/NIH)
Translucence Biosystems (Irvine, CA)
Sunil Gandhi (University of California, Irvine)
Ricardo Azevedo (University of California, Irvine)
Video: iDISCO-cleared whole brain from a Thy1-GFP mouse (Translucence Biosystems)
Show Us Your BRAINs! Photo & Video Contest (Brain Initiative/NIH)
NIH Support: National Institute of Mental Health; National Eye Institute