Optical imaging techniques such as voltage-sensitive dye imaging and intrinsic imaging allow for the record- ing of neuronal activity at high spatio-temporal scales over a large field of view revealing some mesoscopic scale dynamics such as propagating waves. In practice however, the achievable image quality deteriorates significantly away from the point of best focus due to the curvature of the brain, which fundamentally limits the spatial extent of the cortex that can be studied through a single image. To improve the field of view achievable by optical imaging, we developed a new optical system adapted to the curvature of the non-human primate brain in study. This is achieved by using a curved detector in combination with an appropriate optical system of double Gaussian and aspherical lenses. Furthermore, to ensure a uniform and reliable illumination of the cortex, we have designed and built a new illumination system consisting of a ring of LEDs at four different wavebands. This static solution will enable imaging for the first time neuronal activity over a very large field of view (15-20mm) with high spatial and temporal resolution. Preliminary results show a significant increase of the area in focus of object imaged through the custom optics compared with the standard neuronal imaging optics.
Recording brain activity at the mesoscopic scale has a strong potential to unveil many new fundamental neuronal operations. Optical imaging offers a unique opportunity to measure brain activity over a large area with high spatio-temporal resolutions (20 μm x 1 ms). However, two major limitations of this imaging technique partially explain the lack of development in this field. The cortex being non-planar, the field's depth limits the region in focus to a small region close to the center of the field of view. This is particularly significant for the highly curved lissencephalic small cortex of non-human primates that are becoming popular in neuroscience experiments. The ideal technique would be a method that compensates for such curvature; it would enable imaging the whole visual system at once, from the primary to the fifth visual cortices, in small non-human primates. Additionally, the signal-to-noise ratio is strongly degraded by the dynamic evolution of the brain curvature due to physiological rhythms (heartbeat, breathing, etc.). This strongly limits the ability to work at a single-trial level and to unravel the real dynamics of neuronal processing, such as spatio-temporal waves. Here in this project, we present an interdisciplinary approach for imaging of the non-human primate cortex, using technologies from astronomical instrumentation to overcome current technological limits. This will be of interest to a wide neuroscientific audience but also will impact the clinical community interested in mapping the nervous activity at the mesoscopic scale. Our current preliminary development involves redesigning the illumination source and the optical design.
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