PI: Takashi Kozai
Title: CAREER: Uncovering the Impact of Traditional and Novel Chronic Stimulation Modalities on Neural Excitability and Native Neuronal Network Function
Description: The ability to selectively stimulate a small group of neurons has been long desired for basic neuroscience studies as well as for clinical applications. To address this need, the investigator has developed a wireless technology that can precisely stimulate a distinct population of neurons by electrical or light stimulation. Because a balance between excitatory and inhibitory neural activity is important for perception in the brain, a key question is how stimulation impacts this balance. An imbalance between excitatory and inhibitory neuronal activity can lead to cognitive dysfunctions and is a hallmark of autism spectrum disorder. Moreover, brain injuries such as traumatic brain injuries, stroke, and microelectrode implantation have also been shown to disrupt this balance. Therefore, the research goal of this CAREER project is to establish the relationship between different types of stimulation and their impact on excitability of neuronal populations. The project’s educational goal is to train the next wave of investigators with the multidisciplinary skills needed to solve the chronic neural interface challenge. This will be achieved through: 1) integrating examples from this research into an outreach program to Underrepresented Minority Students that focuses on introducing the fundamental principles of the scientific method and engineering design controls and criteria and on demonstrating how science and engineering converge at the neural interface; 2) making neural interface knowledge more widely accessible by the formation of the virtual “Education in Biological and Neuroelectronic Interface Community” (eBioNIC.org) that will be a focal point for providing videos and other training materials; and 3) providing an early platform for hands-on education on integrating Neurobiology and Neural Engineering.
The Investigator’s long-term career vision is to seamlessly integrate the brain and technology in order to enable new approaches to studying long-standing neurobiology questions such as how to repair brain injuries and neurodegenerative diseases. Towards this vision, this CAREER project?s specific goals are to break through traditional limitations of neurostimulation by engineering wireless axons that use specific biomolecules to modulate the activity of a small population of neurons in the brain, and then apply this technology to modulate excitatory-inhibitory neuronal imbalances. The project will employ new optical technologies to solve long-standing questions on the relationship between stimulation technologies and changes to the brain?s excitatory-inhibitory balance. This will be achieved using optical and transgenic methods to determine the cell-type specificity of excitatory and inhibitory neuronal activity, an important parameter that can enhance our physiological understanding of the activated brain region. The project’s guiding hypothesis is that different stimulation modalities will differentially alter spatio-temporal excitatory and inhibitory neuronal activity, which will in turn alter the long-term excitability of nearby neurons in different capacities. The Research Plan is organized under two objectives. THE FIRST Objective is to further engineer this wireless stimulation technology to reliably and repeatably release specific biomolecules including neurotransmitters. Coating technologies will be applied to the wireless axons to release biomolecules during stimulation and recharge by drawing upon endogenously produced biomolecules. THE SECOND Objective is to investigate how stimulation with electrical, optical, wireless-axon, and wireless neurochemical modalities impacts long-term excitatory and inhibitory neuronal excitability using in vivo 2-photon microscopy and genetically encoded fluorescent indicators. In vivo images will be collected from awake head-fixed mice at increasing intervals daily for two weeks and then once a week until 12 weeks. The number, distance, timing and neuronal subtype densities before, during and after electrical stimulation will be examined over time. The method enables tracking of stimulation-induced dynamic changes with high spatial resolution near the electrodes. Research outcomes are expected to have a significant impact on the future design of neural interfaces through the engineering of chronic selective neural stimulation tools with ultra-small free-floating implants that will provide scientists with a new tool for interrogating neuronal networks and creating different sensations in BCIs and through visualization of how stimulation with electrical, optical, wireless, and wireless neurochemical modalities impacts long-term excitatory and inhibitory neural excitability.
Source: National Science Foundation
Term: July 1, 2020 – June 30, 2025 (Estimated)