Abstract - Joel Kubby

We propose to develop a three-photon excitation (3PE) microscope with adaptive optics (AO) for deep brain imaging in live animals. Brain structures such as hippocampus and striatum play essential roles in navigation, decision making, learning and memory, but reside at a depth inaccessible to current optical microscopy. Our proposed microscope will be based on an Olympus FV1200MPE two-photon microscope, supplemented with a low duty cycle (10 MHz), high pulse energy (50 nJ) femto-second (80 fs) fiber laser for 3PE, and an AO system for wavefront sensing and correction. The long wavelength (1.55μm) 3PE will significantly decrease scattering, hence increasing the imaging depth and signal-to-background ratio. AO will correct aberrations due to inhomogeneous refractive indices in brain tissue to achieve better resolution. The 3PE laser will be suitable for common fluorescent proteins with excitation peaks near 517nm (~1.55μm/3), such as EYFP, Venus, and mCitrine. The microscope will enable anatomical and functional imaging of neural circuits with sub-cellular resolution 1,500-1,800μm below the brain surface, 3-5 times deeper than commonly achieved with two-photon microscopy. It will greatly facilitate research on structural alterations (e.g., dendritic spine dynamics) and neuronal activities (e.g., Ca signals) in deep cortical layers and subcortical regions including hippocampus and striatum.

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Principal Investigator Institution Title Abstract
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