Development of Flexible Neural Probes for Stimulation and Recording in the Central Nervous System

The functionality of cortical neurons depends on the strength of its local and long-range synapses and the interpretation of the physical and functional anatomy depends on the understanding of these connections. Optogenetics uses genetic manipulations to insert opsin containing ion channels into neurons. Then light can be used to optically gate ion-transport across the plasma membrane to stimulate or silence spiking activity with greater cellular specificity and spatio-temporal resolution than previously possible. While great progress has been made in the genetic methods used in optogenetics, little progress has been made in improving the devices (optrodes) used to simultaneously photostimulate and record neural activity. In this dissertation we describe the development of a new probe concept based on the integration of micrometer-scale thin film electrodes and associated interconnect wiring on the cylindrical surface of fine optical fibers with tight manufacturing tolerances. The use of optical fibers as probe substrates provides high intensity, multi-spectral light delivery with essentially no coupling loss, as well as the strength and stiffness required for deep-brain applications. High resolution permits a very high electrode count on thin fibers, and high dimensional precision enables accurate 3-D localization of neuronal sources. Moreover, the technology is compatible with high throughput manufacturing at very low cost, an important consideration for wide dissemination of the technology, particularly for linear and 2D-array applications. A second crucial development is the design and implementation of a multi-electrode interface between thin-film wiring on the (cylindrical) probe and state-of-the-art neuro-amplifier and signal processing systems.
Two-channel prototypes have been fabricated and used in preliminary experiments to 1) record photostimulated neural activity in a group of genetically identified neurons in the primate primary visual cortex at the Vanderbilt University School of Medicine (VUSM), and 2) demonstrate source localization in the rat hippocampus at the Baylor College of Medicine (BCM). The prototypes had 15x15 µm2 gold electrodes on 65 µm optical fibers with lengths up to 3 cm. In future work, we propose to further reduce probe diameter to the ~30 µm range to develop probes with advanced functionality and extend the technology to 1- and 2-D arrays.