Implantable Neural Probes for Electrical Recording and Optical Stimulation of Cellular Level Neural Circuitry in Behaving Animals.

Abstract

In order to advance the understanding of brain function, it is critical to monitor how neural circuits work together and perform computational processing. For the past few decades, a wide variety of neural probes have been developed to study the electrophysiology of the brain. This work is focused on two important objectives to improve the brain-computer interface: 1) to enhance the reliability of recording electrodes by optimizing the shank structure; 2) to incorporate optical stimulation capability in addition to electrical recording for applications involving optogenetics. For the first objective, a flexible 64-channel parylene probe was designed with unique geometries for reduced tissue reactions. In order to provide the mechanical stiffness necessary to penetrate the brain, the miniaturized, flexible probes were coated with a lithographically patterned silk fibroin, which served as a biodegradable insertion shuttle. Because the penetration strength is independent from the properties of the probe itself, the material and geometry of the probe structure can be optimally designed without constraints. These probes were successfully implanted into the layer-V of motor cortex in 6 rats and recorded neural activities in vivo for 6 weeks. For the second objective, either optical waveguides or μLEDs were monolithically integrated on the probe shanks for optogenetic applications. Compared to existing methods, this work can offer high spatial-temporal resolution to record and stimulate from even subcellular neural structures. In the experiments using wild type animals, despite optimized recording of spontaneous neural activities, the cells never responded to illumination. In contrast, for the ChR2 expressed animals, light activation of neural activities was extremely robust and local, which phase-locked to the light waveform whenever the cell was close to the light source. In particular, the probes integrated with μLEDs were capable of driving different neural circuit behaviors using two adjacent μLEDs separated only by a 60-μm-pitch. With 3 μLEDs integrated at the tip of each of the 4 probe shanks, this novel optogenetic probe can provide more than 480 million (12!) different spiking sequences at the sub-cellular resolution, which is ideal to manipulate high density neural network with versatility and precision.