The human brain has billions of neurons. Working together, they enable higher-order brain functions such as cognition and complex behaviors. To study these higher-order brain functions, it is important to understand how neural activity is coordinated across various brain regions.
Although techniques such as functional magnetic resonance imaging (fMRI) are able to provide insights into brain activity, they can show only so much information for a given time and area. Two-photon microscopy involving the use of cranial windows is a powerful tool for producing high-resolution images, but conventional cranial windows are small, making it difficult to study distant brain regions at the same time.
Now, a team of researchers led by the Exploratory Research Center on Life and Living Systems (ExCELLS) and the National Institute for Physiological Sciences (NIPS) have introduced a new method for in vivo brain imaging, enabling large-scale and long-term observation of neuronal structures and activities in awake mice.
This method is called the “nanosheet incorporated into light-curable resin” (NIRE) method, and it uses fluoropolymer nanosheets covered with light-curable resin to create larger cranial windows.
“The NIRE method is superior to previous methods because it produces larger cranial windows than previously possible, extending from the parietal cortex to the cerebellum, utilizing the biocompatible nanosheet and the transparent light-curable resin that changes in form from liquid to solid,” says lead author Taiga Takahashi of the Tokyo University of Science and ExCELLS.
In the NIRE method, light-curable resin is used to fix polyethylene-oxide–coated CYTOP (PEO-CYTOP), a bioinert and transparent nanosheet, onto the brain surface. This creates a “window” that fits tightly onto the brain surface, even the highly curved surface of the cerebellum, and maintains its transparency for a long time with little mechanical stress, allowing researchers to observe multiple brain regions of living mice.
“Additionally, we showed that the combination of PEO-CYTOP nanosheets and light-curable resin enabled the creation of stronger cranial windows with greater transparency for longer periods of time compared with our previous method. As a result, there were few motion artifacts, that is, distortions in the images caused by the movements of awake mice,” says Takahashi.
The cranial windows allowed for high-resolution imaging with sub-micrometer resolution, making them suitable for observing the morphology and activity of fine neural structures.
“Importantly, the NIRE method enables imaging to be performed for a longer period of more than 6 months with minimal impact on transparency. This should make it possible to conduct longer-term research on neuroplasticity at various levels—from the network level to the cellular level—as well as during maturation, learning, and neurodegeneration,” explains corresponding author Tomomi Nemoto at ExCELLS and NIPS.
This study is a significant achievement in the field of neuroimaging because this novel method provides a powerful tool for researchers to investigate neural processes that were previously difficult or impossible to observe. Specifically, the NIRE method’s ability to create large cranial windows with prolonged transparency and fewer motion artifacts should allow for large-scale, long-term, and multi-scale in vivo brain imaging.
“The method holds promise for unraveling the mysteries of neural processes associated with growth and development, learning, and neurological disorders. Potential applications include investigations into neural population coding, neural circuit remodeling, and higher-order brain functions that depend on coordinated activity across widely distributed regions,” says Nemoto.
In sum, the NIRE method provides a platform for investigating neuroplastic changes at various levels over extended periods in animals that are awake and engaged in various behaviors, which presents new opportunities to enhance our understanding of the brain’s complexity and function.
More information: Taiga Takahashi et al, Large-scale cranial window for in vivo mouse brain imaging utilizing fluoropolymer nanosheet and light-curable resin, Communications Biology (2024).
Journal information: Communications Biology
News
Studies detail high rates of long COVID among healthcare, dental workers
Researchers have estimated approximately 8% of Americas have ever experienced long COVID, or lasting symptoms, following an acute COVID-19 infection. Now two recent international studies suggest that the percentage is much higher among healthcare workers [...]
Melting Arctic Ice May Unleash Ancient Deadly Diseases, Scientists Warn
Melting Arctic ice increases human and animal interactions, raising the risk of infectious disease spread. Researchers urge early intervention and surveillance. Climate change is opening new pathways for the spread of infectious diseases such [...]
Scientists May Have Found a Secret Weapon To Stop Pancreatic Cancer Before It Starts
Researchers at Cold Spring Harbor Laboratory have found that blocking the FGFR2 and EGFR genes can stop early-stage pancreatic cancer from progressing, offering a promising path toward prevention. Pancreatic cancer is expected to become [...]
Breakthrough Drug Restores Vision: Researchers Successfully Reverse Retinal Damage
Blocking the PROX1 protein allowed KAIST researchers to regenerate damaged retinas and restore vision in mice. Vision is one of the most important human senses, yet more than 300 million people around the world are at [...]
Differentiating cancerous and healthy cells through motion analysis
Researchers from Tokyo Metropolitan University have found that the motion of unlabeled cells can be used to tell whether they are cancerous or healthy. They observed malignant fibrosarcoma [...]
This Tiny Cellular Gate Could Be the Key to Curing Cancer – And Regrowing Hair
After more than five decades of mystery, scientists have finally unveiled the detailed structure and function of a long-theorized molecular machine in our mitochondria — the mitochondrial pyruvate carrier. This microscopic gatekeeper controls how [...]
Unlocking Vision’s Secrets: Researchers Reveal 3D Structure of Key Eye Protein
Researchers have uncovered the 3D structure of RBP3, a key protein in vision, revealing how it transports retinoids and fatty acids and how its dysfunction may lead to retinal diseases. Proteins play a critical [...]
5 Key Facts About Nanoplastics and How They Affect the Human Body
Nanoplastics are typically defined as plastic particles smaller than 1000 nanometers. These particles are increasingly being detected in human tissues: they can bypass biological barriers, accumulate in organs, and may influence health in ways [...]
Measles Is Back: Doctors Warn of Dangerous Surge Across the U.S.
Parents are encouraged to contact their pediatrician if their child has been exposed to measles or is showing symptoms. Pediatric infectious disease experts are emphasizing the critical importance of measles vaccination, as the highly [...]
AI at the Speed of Light: How Silicon Photonics Are Reinventing Hardware
A cutting-edge AI acceleration platform powered by light rather than electricity could revolutionize how AI is trained and deployed. Using photonic integrated circuits made from advanced III-V semiconductors, researchers have developed a system that vastly [...]
A Grain of Brain, 523 Million Synapses, Most Complicated Neuroscience Experiment Ever Attempted
A team of over 150 scientists has achieved what once seemed impossible: a complete wiring and activity map of a tiny section of a mammalian brain. This feat, part of the MICrONS Project, rivals [...]
The Secret “Radar” Bacteria Use To Outsmart Their Enemies
A chemical radar allows bacteria to sense and eliminate predators. Investigating how microorganisms communicate deepens our understanding of the complex ecological interactions that shape our environment is an area of key focus for the [...]
Psychologists explore ethical issues associated with human-AI relationships
It's becoming increasingly commonplace for people to develop intimate, long-term relationships with artificial intelligence (AI) technologies. At their extreme, people have "married" their AI companions in non-legally binding ceremonies, and at least two people [...]
When You Lose Weight, Where Does It Actually Go?
Most health professionals lack a clear understanding of how body fat is lost, often subscribing to misconceptions like fat converting to energy or muscle. The truth is, fat is actually broken down into carbon [...]
How Everyday Plastics Quietly Turn Into DNA-Damaging Nanoparticles
The same unique structure that makes plastic so versatile also makes it susceptible to breaking down into harmful micro- and nanoscale particles. The world is saturated with trillions of microscopic and nanoscopic plastic particles, some smaller [...]
AI Outperforms Physicians in Real-World Urgent Care Decisions, Study Finds
The study, conducted at the virtual urgent care clinic Cedars-Sinai Connect in LA, compared recommendations given in about 500 visits of adult patients with relatively common symptoms – respiratory, urinary, eye, vaginal and dental. [...]
