Optical and electrophysiological technologies for monitoring cortex-wide brain activity

Abstract

Recording cortex-wide brain activity and decoding the brain’s neural computations are required to mediate behaviors. Such an understanding will help formulate better treatments for neurological disorders and improve the quality of life. Technologies for sensing neural activities have been continuously developed over the past century. These technologies have gradually improved to recording from larger brain regions at high temporal and spatial resolution. Miniaturized devices have been developed for performing such imaging in freely-behaving animals. Along these lines, this thesis first aimed to develop a high-accessibility neural activity sensing technology and developed a fully desktop-fabricated flexible Graphene electrocorticography (ECoG) arrays that can be completely built using commonly used laboratory tools without the need for specialized cleanroom facilities. The ECoG arrays could be implanted chronically for up to 180 days allowing high-quality measurement surface field potentials. Building on this work, I developed a 3D-printed transparent ECoG array that simultaneously performs ECoG recordings and mesoscale Calcium (Ca2+) imaging from multiple sites. This device allowed the combination of high temporal resolution electrophysiological measurements with high spatial resolution optical readout of neural activities. In in vivo recording, the 3D-printed ECoG recorded stimuli-evoked and anesthesia drug-induced brain activity in mice and showed strong correlations between the optical and electrical signals with a cross-correlation factor > 75%. In the third aim, I developed a miniaturized micro-camera array microscope (mini-MCAM) for cortex-wide Calcium imaging at single-cell resolution in head-fixed or freely behaving mice. Mini-MCAM is an array of 4 microcameras generating a large computationally stitched FOV of 30-40 mm2 with a central resolution of 9.9 µm. The mini-MCAM recorded spontaneous brain activities at head-fixed and freely behaving states where distinctive neurons’ activities were recorded and identified. In this thesis, all three neural activity sensing technologies share a common goal to improve the existing neural activity sensing technologies and accelerate fundamental neuroscience research, which will bring new insights into the brain.