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Science and Mathematics

Cracking Brain Complexity through Multiphoton Imaging

February 20, 2020 at 3:30pm5:00pm EST

Physics Building, 202 / 204

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The Department of Physics welcomes Murat Yildirim, a postdoctoral associate at the Picower Institute for Learning and Memory at the MIT for their  weekly colloquia. He holds a PhD degree from UT Austin and he received his B.Sc. and M.Sc. degrees from Middle East Technical University in Turkey, all in Mechanical Engineering. His current research interests are developing next generation multiphoton systems to study the structure and function of the brain with various biological systems and models spanning from cerebral organoids, to small animals, to humans through their interaction with femtosecond laser pulses for the diagnosis, characterization, and treatment of specific brain disorders to positively impact human mental health. He is a member of SPIE, OSA, and SfN. This speaker is a candidate for a faculty position in the Department of Physics, part of the cluster hiring initiative in the BioInspired Institute.

Abstract: Two-photon microscopy has become the workhorse of tissue imaging in the life sciences, particularly in neuroscience, where it is used to perform high-resolution, structural and functional brain imaging and stimulation in various biological systems and models. However, two-photon microscopy has severe limitations for deep brain imaging due to absorption and scattering at greater depths, as well as photodamage and toxicity accompanying higher laser power at the brain surface. Therefore, imaging and stimulating neuronal populations in deep cortical and subcortical areas with two-photon microscopy is challenging. In this talk, I will discuss the design, implementation, and applications of two- and three-photon microscopy for performing high-resolution, damage-free, and deep tissue imaging for clinical and neuroscience applications. In the first part of my talk, I will describe the design and implementation of table-top and endoscopic multiphoton microscopes for the treatment of vocal fold scarring. Vocal fold scarring is a common side effect of surgical treatment of laryngeal cancer and current treatment options are based on blind injection of biomaterials to restore their viscoelasticity. To address this challenge, I have developed a treatment method in which an injection space is created through sub-epithelial ablation of a planar region assisted with multiphoton imaging.

In the second part of my talk, I will describe the design and optimization of a three-photon microscope for live, in vivo, damage-free imaging at a sub-cellular resolution in deep layers of the cortex in awake mice. Specifically, I will demonstrate the application of the microscope for imaging structural features and functional evoked calcium responses of neurons through the entire cerebral cortex down to the subplate of primary and higher visual areas in awake mice. In the last part of my talk, I will demonstrate the use of three-photon microscopy to perform high-resolution deep-tissue imaging in intact cerebral organoids. Human cerebral organoids are unique in their development of progenitor-rich zones akin to ventricular and subventricular zones from which neuronal progenitors differentiate and migrate radially to generate the layers of the cortex. However, analyses of cerebral organoids thus far have been performed in sectioned tissue, thus providing only static two-dimensional views of the spatiotemporal dynamics of organoid development. Here, I will demonstrate label-free, four-dimensional three-photon imaging of intact organoids in fixed and live conditions to assess the key components of early neurogenesis such as cell migration in Rett syndrome. These technologies will enable my lab to crack the brain complexity through the study of its structure and function in various biological systems and models such as behaving mice and cerebral organoids in healthy and disease states.



This event was first published on January 27, 2020 and last updated on January 28, 2020.

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