Abstract
A major open challenge in neuroscience is the ability to measure and perturb neural activity in vivo from well defined neural sub-populations at cellular resolution anywhere in the brain. However, limitations posed by scattering and absorption prohibit non-invasive multi-photon approaches for deep (>2mm) structures, while gradient refractive index (GRIN) endoscopes are relatively thick and can cause significant damage upon insertion. Here, we present a novel micro-endoscope design to image neural activity at arbitrary depths via an ultra-thin multi-mode optical fiber (MMF) probe that has 5-10X thinner diameter than commercially available micro-endoscopes. We demonstrate micron-scale resolution, multi-spectral and volumetric imaging. In contrast to previous approaches, we show that this method has an improved acquisition speed that is sufficient to capture rapid neuronal dynamics in-vivo in rodents expressing a genetically encoded calcium indicator (GCaMP). Our results emphasize the potential of this technology in neuroscience applications and open up possibilities for cellular resolution imaging in previously unreachable brain regions.
Highlights
Multi-photon surface based imaging techniques have been successfully applied in neuroscience applications to image neurons and their activity at depths up to 1.6 mm relative to the cortical surface [1, 2]
SNR and enhancement factor Following the procedure described in section 3.1, we constructed a high dynamic range (HDR) image of the fiber after generating a spot at a single location (Fig. 5(a))
We found that the distribution of Enhancement Factor (EF) values can vary significantly as a function of the coupling at the proximal side
Summary
Multi-photon surface based imaging techniques have been successfully applied in neuroscience applications to image neurons and their activity at depths up to 1.6 mm relative to the cortical surface [1, 2]. Lie beyond 1.6mm, especially in larger animals (e.g., ventral regions in non-human primates are 30mm deep relative to the dorsal surface). Requirements for deep imaging deep in non-human primates (NHP) can be different compared to deep imaging systems designed for rodents. GRIN lenses typically have a large diameter (0.5-1mm) and are difficult to fabricate at smaller diameters at long lengths due to their fragility. Inserting such large diameter probes into the brain can cause significant damage and tissue displacement, which is why a common practice is to aspirate the brain above the region of interest to be imaged [7]
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