M.Sc Thesis

M.Sc StudentLevinsky Alexandra
SubjectHolographic Fiber Bundle System for Patterned
Optogenetic Activation of Large-Scale Neuronal
DepartmentDepartment of Autonomous Systems and Robotics
Supervisors PROF. Shy Shoham
Full Thesis textFull thesis text - English Version


The brain is a complex organ due to its vast number of cells (neurons) and their interconnectivity. Although much is known about the nature of its structural connectivity, far less is known about the nature of information passing through these connections, or the brain's 'functional connectivity'. Thus, developing tools to decipher functional connectivity is a major target in brain research, requiring the combination of the ability to precisely evoke neuronal activity and to readout throughout the entire brain the result of this activity. Optogenetics is a technique that allows to genetically modify neurons such that they can be activated with light while functional Magnetic Resonance Imaging (fMRI) offers the ability to image function across the whole-brain; the combination of the two techniques allows interrogating functional connectivity in the living animal brain.

To take advantage of optogenetic fMRI, photo-stimulation systems for spatially precise (patterned) light delivery to the brain are required. Although in recent years systems for delivering patterned light to deep brain structures were introduced, currently available solutions are not MRI-compatible, not energy efficient and partially lack the pattern flexibility. Here, we present an MRI-compatible fiber bundle-based holographic projection system for efficient high spatiotemporal control of neural circuits. A pattern is generated by means of computer generated holography and projected using a spatial light modulator (SLM). During the calibration process the transformation matrices between the SLM plane and the fiber bundle input and output planes are characterized, enabling the activation of only particular fiber or sets of fibers to create a desirable pattern to be delivered to the brain. This system combines high spatiotemporal resolution with energy-efficient pattern generation and can also be coupled to 3D waveguide arrays for deep brain stimulation. We also present physiological data from cortical cell cultures, which demonstrate our system's ability to optogenetically control the activity of neurons.