Multifunctional Wireless Gut-Brain Neurotechnology

Abstract

The complexity of the brain is well known, in that it uses specially organized neural circuits to interact with the external world. Besides external stimuli, the brain also receives, integrates, and responds to sensory signals emerging from internal organs of the body through the network of the peripheral nervous system. Although these nerve signals are subliminal and cannot be consciously detected or controlled, they play a profound role in maintaining a homeostatic state. Recent evidence also suggests that interoceptive signals can impact higher level cognitive functions. The anatomical, functional, and molecular details about these brain-body pathways are beginning to be deciphered, but a lot remains to be uncovered. Cutting edge neurobiological tools like optogenetics, chemogenetics, and activity-based sensors have revolutionized studies of the brain. However, application of these methodologies for studies of brain-body circuits is reliant on engineered devices that support these sophisticated functions in peripheral organs too. Studying interoceptive circuits in a causal fashion in behaving animals, thus, requires advanced multifunctional implantable neurotechnologies that can be deployed at multiple sites spanning regions in the brain and the peripheral organ of interest. This thesis aims to bridge this unmet technological need. This work presents a collection of advances that overcome thermomechanical constraints of fiber drawing and allow processing of traditionally non-drawable components. These advances yielded multifunctional probes that allow depth specific optical, electrical, and pharmacological probing of neural circuits in the brain, while also being compatible with brain-wide functional magnetic resonance imaging techniques. The same underlying design principles have also made possible fiber-based miniaturized electrochemical probes for performing electrocatalytic reactions in the brain to deliver transient, gaseous neurotransmitters, such as NO, through controlled generation and delivery in-vivo. Finally, wireless microelectronic fibers that combine the scalability and mechanical versatility of thermally drawn polymer fibers with the sophistication of microelectronic chips for organs as diverse as the brain and the gut were developed. This approach produces meters-long continuous fibers that can integrate light sources, electrodes, thermal sensors, and microfluidic channels in a miniature footprint. Paired with custom-fabricated control module, the fibers wirelessly deliver light for optogenetics and transfer data for physiological recording. This technology was validated by modulating the mesolimbic reward pathway in the mouse brain and the anatomically challenging intestinal lumen to demonstrate wireless control of sensory epithelial cells and vagal afferents that guide animal’s feeding and reward behaviors.