M.Sc Thesis

M.Sc StudentZoubi Alaa
SubjectAdvances towards 3D Photo-Absorber Mediated Neural
Excitation: Optical and Acoustic Characteristics
DepartmentDepartment of Biomedical Engineering
Supervisor PROF. Shy Shoham
Full Thesis textFull thesis text - English Version


Patterned photo-stimulation offers a promising path towards effective control of distributed neuronal circuits, but three-dimensional control remains challenging. In this work we studied the feasibility and governing principles of Photo-Absorber Induced Neural-Thermal Stimulation (PAINTS), a novel photo-excitation method based on light absorption by exogenous photo-absorbers dispersed in the vicinity of neurons. We projected light patterns using an infrared (IR) femtosecond laser, inducing microscopic thermal transients, which are found to have sub-msec decay times and thereby stimulating adjacent cells with high spatiotemporal resolution. We show that PAINTS activation thresholds for different laser pulse durations (0.02 to 1msec) consistently follow the Lapicque strength-duration formula. By comparing the results obtained with the femtosecond laser with those obtained using a continuous wave (CW) laser system, we found that the femtosecond setup has an order of magnitude lower energy thresholds ( <50nJ), suggesting the possibility of an auxiliary excitation mechanism. To understand this excitation mechanism, photo-acoustic measurements were performed, revealing the generation of characteristic ultrasonic signals in the ~1MHz range around the absorbers upon laser heating, which is putatively associated with a laser-induced transient cavitation. The PA signals were characterized and a comparison between PA thresholds with stimulation thresholds was performed revealing similar behavior of both of the curves, the obtained results suggest this acoustic response as a novel physical neurostimulation mechanism.

Next, we explored the adaptation of PAINTS to three dimensions (3D) selective excitation across large neuronal populations, by implementing an efficient 3D computational module for the holographic display system, and a piezo-based 3D microscope for functional imaging of the distributed network activity patterns.  Our study provides further support that holographically patterned PAINTS could potentially provide a means for minimally intrusive control over neuronal dynamics with a high level of spatial and temporal selectivity.