Improving technologies for the manipulation and measurement of brain activity

Abstract

The ability to measure and manipulate brain activity is integral to much of neuroscience. Several modalities can be used to transmit information between the brain tissue and the experimental device, each with its own benefits and drawbacks. In this thesis, I treat two major thrusts towards emerging technologies that improve upon optical information transmission modalities. I examine light propagation in the brain, with a focus on its importance to optogenetic manipulation of neural activity. Optogenetics is emerging as a powerful tool for neural activity manipulation: it is fast, can be genetically targeted to specific cell types, and can provide bidirectional control (inhibition or stimulation). Manipulation requires transmitting light from an experimental device to the light sensitive proteins that modulate the cell's activity. The brain is a highly scattering, highly absorbing, nonhomogeneous medium.

I created a Monte Carlo code to simulate light's propagation through this medium and used it to guide the design of optogenetic stimulators and predict the in vivo performance of new optogenetic proteins. I designed and computationally evaluated the performance of a new kind of imager-referred to as an Implantable Light Field Microimager (ILM) -- when used to measure neural activity reported by genetically encoded calcium sensors. Fluorescent reporters of physiological activity are already important tools in the study of neural dynamics, but recording the optical signals with sufficient temporal and spatial resolution -- especially in deep brain structures --

remains challenging due to the optical properties of brain tissue. The ILM fuses recent developments in light field imaging and computational photography with an algorithm that uses priors to solve the otherwise-underconstrained reconstruction problem. My simulations indicate that such a device would be effective at achieving single-cell resolution of neural activity at high speeds, with minimal tissue displacement and impact on brain temperatures -- an often overlooked aspect of brain implants that can have major impacts on neural activity.