Curved Implantation of Flexible Microelectrode Arrays for High-Density Mapping of Nonlinear Brain Structures and Circuits

Project Summary The brain is nature’s most sophisticated signal-processing system. Unlike human-made integrated circuits, the brain circuits organize in a complex three-dimensional and intertwined manner, which makes it challenging to spatially resolve neuronal activities. Among all available neural recording technologies, penetrating neural

probes hold great promise and are vital to neuroscience research. In common practice, neural probes are linearly inserted into the brain to map the local activity, which, however, can only probe a single spot in the targeted brain region. An entire circuit or structure can be mapped by deploying multiple probes, but the spatial resolution is

modest. To date, how to spatially resolve single-unit activities from nonlinearly organized brain structures and circuits is still a challenge. Here, we propose to fill the technological gap via a nonlinear probe implantation modality. In contrast to the conventional linear implantation, we will conformally deploy high-density

microelectrode arrays along designated curved brain circuits or structures with minimal surgical lesions. Ultraflexible neural probes with high electrode density will be designed accordingly to obtain the optimal nonlinear implantation outcome. The proposed technology will be fulfilled via three Aims: In Aim 1, we will

develop the implantation apparatus and optimize the probe design using an in-vitro test platform; In Aim 2, we will evaluate and optimize the nonlinear implantation in vivo and characterize the surgical lesion and biocompatibility of the probes; in Aim 3, we will systematically examine the nonlinear probe in single-unit

neuronal recording and demonstrate its usefulness in studying the place codes of the mouse hippocampus. In our preliminary study, we validated the feasibility of the proposed method by deploying nonlinear probes along the longitudinal axis of the mouse hippocampus, a well-known nonlinear structure in the brain. Precise targeting,

low surgical lesion, and chronic single-unit tracking were shown. The technology, if successful, will significantly increase the spatial resolution of brain mapping along nonlinear circuits or brain structures, make the hard-to- access brain regions within reach, offer alternative routes toward designated brain regions, and offer a

generalizable approach for other brain interventions. In all, we believe the nonlinear delivery of neural probes enabled by this project will be a valuable modality complementary to the conventional linear implantation for both basic and translational neurosciences.