Towards Artefact-Free Closed-Loop Optogenetic Platforms

Abstract

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. However, optogenetic systems can also be prone to interference (artefact) between the optical stimulation and the electrical recording depending on the architecture. The thesis provides a review of the different architectures and components of closed-loop optogenetic systems that have been developed in the field, as well as a thorough description of the development process and usability of customised platforms developed as part of the Controlling Abnormal Network Dynamics using Optogenetics (CANDO) project. The systems were developed by incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a Microcontroller Unit (MCU) and experimental control via a PC interface. Commercial components were also included to validate performance, with the ultimate aim of translating this approach to humans. In the meantime, the systems are flexible and expandable for use in a variety of preclinical neuroscientific applications. This work focuses on two such platforms; The first consists of a CANDO Control System (CS) that interfaces with up to four CANDO head-stages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes. Control of the hardware, inbuilt algorithms and data acquisition is enabled via the CANDO GUI (Graphical User Interface). The functionality of the system has been verified through bench-top testing and modulating neuronal oscillations in vitro and in vivo. As for the second platform, it focuses on maintaining a compact size and low power consumption targeting freely moving experiments. The thesis adumbrates the hardware, firmware and software architectures, the neurophysiological validation of their operation and analyses both experimentally and through simulations the interference (artefact) between the optical stimulation and the electrical recording. The outcomes of the artefact studies have been presented as design considerations and mitigation techniques towards the development of artefact-free closed-loop optogenetic platforms.