Tools that allow neuroscientists to record and quantify functional activity in the living brain are in great demand. Traditionally, researchers have used techniques such as functional magnetic resonance imaging, but this method cannot record neuronal activity with high spatial resolution or in moving subjects. In recent years, a technology called optogenetics has shown tremendous success in recording the neuronal activity of animals in real time with unique neuronal resolution. Optogenetic tools use light to control neurons and record signals in tissue genetically modified to express light-sensitive and fluorescent proteins. However, the existing technologies for imaging brain light signals have drawbacks in terms of size, imaging speed or contrast which limit their applications in experimental neuroscience.
A technology called light-film fluorescence imaging shows promise for imaging brain activity in 3D with high speed and contrast (overcoming the multiple limitations of other imaging technologies). In this technique, a thin sheet of laser light (sheet of light) is directed through a region of brain tissue of interest, and reporters of fluorescent activity in brain tissue respond by emitting fluorescence signals that microscopes can detect. Scanning a layer of light in the tissue enables high-speed, high-contrast volumetric imaging of brain activity.
Currently, the use of light-film fluorescence brain imaging with non-transparent organisms (such as a mouse) is difficult due to the size of the device required. To make experiments with non-transparent animals and, in the future, free-moving animals feasible, researchers will first have to miniaturize many components.
A key part of miniaturization is the light sheet generator itself, which needs to be inserted into the brain and therefore needs to be as small as possible to avoid moving too much brain tissue. In a new study published in Neurophotonics, an international team of researchers from the California Institute of Technology (United States), the University of Toronto (Canada), the University Health Network (Canada), the Max Planck Institute of Microstructure Physics (Germany) and Advanced Micro Foundry (Singapore) has developed a miniature light sheet generator, or photonic neural probe, which can be implanted in the brain of a living animal.
Researchers used nanophotonic technology to create ultra-thin silicon-based photonic neural probes that emit multiple thin, addressable layers of light with thicknesses <16 micrometers over propagation distances of 300 microns in free space. When tested in brain tissue from mice genetically engineered to express fluorescent proteins in their brains, the probes allowed researchers to image areas as large as 240 µm × 490 µm. In addition, the contrast level of the image was higher than that of another imaging method called epifluorescence microscopy.
Describing the importance of his team’s work, lead author of the study, Wesley Sacher, said: “This new implantable photonic neural probe technology to generate light sheets in the brain circumvents many of the constraints that have limited the ‘Use of light sheet fluorescence imaging in experimental neuroscience. We predict that this technology will lead to new variants of light sheet microscopy for deep brain imaging and behavioral experiments with free-moving animals. “
Such variations would be a boon to neuroscientists seeking to understand how the brain works.
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