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Title: Microsphere enhanced optical neural stimulation and photoacoustic neural recording
Authors: Cao, Fei
Degree: Ph.D.
Issue Date: 2021
Abstract: Understanding the roles of neurons on behavior requires precise perturbation and fast reading of neural activity during ongoing behavior. Optical techniques stand out of other modalities regarding the cell-type/circuit specificity and the ability to both polarize and depolarize neurons with high spatiotemporal resolution. Optogenetics, relying on fiber optics and light-sensitive neural actuators, has revolutionized the neural stimulation field making it possible to precisely investigate a certain neural function in a casual manner. Optical reading, based on neural-activity-sensitive indicators integrated with fluorescent sensors and working with various optical configurations, brings molecular-level understanding of brain functions. Despite tremendous developments in superficial cortex, the inherent strong light attenuation in tissue remains a major challenge for interrogation of deep brain regions. The opaque scalp and skull are first two parcloses that block light to penetrate the brain. The brain tissue itself, is lipid rich and highly turbid in which photons can hardly go very far (more than 200μm) ballistically. For optical stimulation, conventional optogenetics uses a fiber inserted into the cortex for delivering sufficient light power to a specific brain region. Effects of tissue scattering is added to the natural conical divergence of light from the fiber tip output, making the power density exponentially reduced to below the threshold which is needed to influence neural function in a sufficient brain region to induce behavior. In this case, strong power density is always required (>100mW/mm2) at the fiber tip for successfully driving a behavior, which results in several side effects, such as heat induced neural damage and "escaped" photons induced retina excitation and background noise behaving. For optical recording, non-ballistic photons act as major role in blurring an image and decrease the signal-to­noise ratio. The imaging depth and recording sensitivity is therefore greatly limited. In this thesis, efforts are made to circumvent the scattering induced light attenuation in brain tissue in both stimulation and recording aspects. Firstly, a microsphere-enhanced optogenetic method is demonstrated exploiting the photonic nanojet effect. The converging profile, i.e., the photonic nanojet is simulated regarding various microsphere sizes and refractive indices to select a most appropriated sphere parameter for experiments. Then by using the transparent polystyrene microsphere, the enhancing ability is studied systematically, from in vitro, ex vivo, to in vivo demonstrations. Results show that microspheres facilitate driving comparable neural response and behavior with much less stimulation power. Secondly, a wearable photoacoustic imaging device for neural calcium imaging is designed and fabricated. The photoacoustic effect is introduced and exploited expecting less scattering from the acoustic side compared to pure optics. Both in vitro and in vivo studies are conducted demonstrating feasibility of the idea. The great potential for combining these two studies in this thesis to form a closed-loop neural interrogation technique is finally discussed to open other possibilities in neuroscience research.
Subjects: Optogenetics
Hong Kong Polytechnic University -- Dissertations
Pages: xxv, 97 pages : color illustrations
Appears in Collections:Thesis

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