Prototype NIR Ca2+ indicators into refined tools that can be applied for neuronal activity imaging in model organisms
One of the major challenges facing the BRAIN initiative is the development of technologies that will enable the recording of neural activity throughout the entire volume of a rodent brain. Optical imaging approaches for recording of neural activity in model organisms have already proven to be highly effective, but are generally limited to imaging of activity near the brain surface. Two strategies for using optical recording approaches to reach deeper in the brain are: (1) Near-infrared fluorescence imaging; and (2) photoacoustic imaging. Near-infrared light penetrates deeper into tissue than visible light due to decreased scattering and the minimal absorbance of hemoglobin and water at these wavelengths. Photoacoustic imaging is amenable to deeper tissue imaging because the signal is an ultrasonic wave that travels through tissue relatively unobstructed. Notably, the combination of photoacoustic imaging with near-infrared excitation light is a particularly promising approach for imaging deep into the rodent brain. Getting light into, and signals out of, the brain is only part of the challenge of optical imaging of neural activity. The other major part of the challenge is converting the effectively “invisible” electrochemical activity of neurons into signal changes that can be detected with an appropriate imaging modality. A particularly powerful approach for converting electrochemical changes into optical signals is to use transgenic animals expressing genetically encoded indicators. Such indicators are naturally colored proteins that have been engineered to change their color (i.e., absorbance or fluorescence) in response to the chemical changes associated with the firing of an action potential. We have been presented with a fortuitous opportunity to develop the first examples of neural activity indicators based on near-infrared proteins. The resulting indicators will be suitable for both fluorescence and photoacoustic imaging, and will therefore revealing activity deeper in the brain than is currently possible and accelerate progress towards the ultimate goals of the BRAIN initiative.
Robert Campbell , University of Alberta
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