Rapid whole-brain imaging with single cell resolution

April 17, 2014

A major challenge of systems biology is understanding how phenomena at the cellular scale correlate with activity at the organism level. A concerted effort has been made especially in the brain, as scientists are aiming to clarify how neural activity is translated into consciousness and other complex brain activities. One example of the technologies needed is whole-brain imaging at single-cell resolution. This imaging normally involves preparing a highly transparent sample that minimizes light scattering and then imaging neurons tagged with fluorescent probes at different slices to produce a 3D representation. However, limitations in current methods prevent comprehensive study of the relationship. A new high-throughput method, CUBIC (Clear, Unobstructed Brain Imaging Cocktails and Computational Analysis), published in Cell, is a great leap forward, as it offers unprecedented rapid whole-brain imaging at single cell resolution and a simple protocol to clear and transparentize the brain sample based on the use of aminoalcohols.

In combination with light sheet fluorescence microscopy, CUBIC was tested for rapid imaging of a number of mammalian systems, such as mouse and primate, showing its scalability for brains of different size. Additionally, it was used to acquire new spatial-temporal details of gene expression patterns in the hypothalamic circadian rhythm center. Moreover, by combining taken from opposite directions, CUBIC enables whole imaging and direct comparison of brains in different environmental conditions.

CUBIC overcomes a number of obstacles compared with previous methods. One is the clearing and transparency protocol, which involves serially immersing fixed tissues into just two reagents for a relatively short time. Second, CUBIC is compatible with many fluorescent probes because of low quenching, which allows for probes with longer wavelengths and reduces concern for scattering when whole brain imaging while at the same time inviting multi-color imaging. Finally, it is highly reproducible and scalable. While other methods have achieved some of these qualities, CUBIC is the first to realize all.

CUBIC provides information on previously unattainable 3D gene expression profiles and neural networks at the systems level. Because of its rapid and high-throughput imaging, CUBIC offers extraordinary opportunity to analyze localized effects of genomic editing. It also is expected to identify neural connections at the whole brain level. In fact, last author Hiroki Ueda is optimistic about further application to even larger mammalian systems. "In the near future, we would like to apply CUBIC technology to whole-body imaging at single cell resolution".

Explore further: Movies synchronize brains

Related Stories

Movies synchronize brains

April 1, 2014
When we watch a movie, our brains react to it immediately in a way similar to other people's brains.

Seeing the brain at greater depth

August 9, 2013
Brain tissue is opaque, so classical microscopy methods require slicing the brain into ultra-thin slivers to allow light to shine through. Techniques have been developed to enhance brain tissue transparency, but the chemicals ...

Precision drugs sought for anxiety disorders

March 26, 2014
Researchers in the University of Helsinki, Finland, are striving to find out how cell communication regulating kainate receptors contribute to the susceptibility towards anxiety disorders. The intention is to also develop ...

Capturing brain activity with sculpted light

September 9, 2013
Scientists at the Campus Vienna Biocenter (Austria) have found a way to overcome some of the limitations of light microscopy. Applying the new technique, they can record the activity of a worm's brain with high temporal ...

Neutrons help visualising materials

April 8, 2014
New imaging methods will offer new possibilities to physicists, material scientists, engineers, palaeontologists, archaeologists, and others, so that they can obtain better information on their objects of study.

Recommended for you

'Residual echo' of ancient humans in scans may hold clues to mental disorders

July 26, 2017
Researchers at the National Institute of Mental Health (NIMH) have produced the first direct evidence that parts of our brains implicated in mental disorders may be shaped by a "residual echo" from our ancient past. The more ...

Laser used to reawaken lost memories in mice with Alzheimer's disease

July 26, 2017
(Medical Xpress)—A team of researchers at Columbia University has found that applying a laser to the part of a mouse brain used for memory storage caused the mice to recall memories lost due to a mouse version of Alzheimer's ...

Cellular roots of anxiety identified

July 26, 2017
From students stressing over exams to workers facing possible layoffs, worrying about the future is a normal and universal experience. But when people's anticipation of bad things to come starts interfering with daily life, ...

Cognitive cross-training enhances learning, study finds

July 25, 2017
Just as athletes cross-train to improve physical skills, those wanting to enhance cognitive skills can benefit from multiple ways of exercising the brain, according to a comprehensive new study from University of Illinois ...

Brain disease seen in most football players in large report

July 25, 2017
Research on 202 former football players found evidence of a brain disease linked to repeated head blows in nearly all of them, from athletes in the National Football League, college and even high school.

Zebrafish study reveals clues to healing spinal cord injuries

July 25, 2017
Fresh insights into how zebrafish repair their nerve connections could hold clues to new therapies for people with spinal cord injuries.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.