|Drs. James McNamara (Neurobiology), Pei Zhou (Biochemistry) and Robert Anthony Mook (Medicine)||Biochemical and Structural Characterization of Inhibitors of TrkB Signaling
Temporal lobe epilepsy (TLE) is a potentially devastating form of human epilepsy for which there is no prevention or cure. A single seizure can disrupt the TrkB signaling pathway, which initiates a chain reaction causing full-on epilepsy. If we can inhibit this chain reaction, we can prevent a single seizure from becoming a devastating illness. This project will explore molecules that inhibit this chain reaction in hopes of finding a prevention method.
|Drs. Sina Farsiu and Marc Sommer (Biomedical Engineering) and Lejla Vajzovic (Ophthalmology)||Psychophysics-Guided Signal Processing for Retinal Prosthetics
A visual prosthesis, or “bionic eye,” has provided some visual function to patients who were completely blind prior to implantation. A small camera worn externally takes pictures, converts them to electronic signals and transmits them to an implantable retinal prosthesis. The resulting image has limited resolution due to hardware-design issues, and improving it would require costly development and approval of new devices. This project seeks to improve image resolution through advanced software design, a non-invasive, cost-efficient method that could be adapted to improve the vision of patients with retinal prostheses.
|Drs. Tobias Overath (Psychology & Neuroscience), Josh Stohl and Leslie Collins (Electrical & Computer Engineering) and Michael Murias (DIBS)||Optimizing Cochlear Implant Sound Processor Configurations via Neural Response Properties to Improve Speech Comprehension
Nearly 1 million Americans are functionally deaf and an additional 400,000 are deaf in one ear. The cochlear implant (CI) is the most successful sensory prosthetic implant to help them regain hearing; about 500,000 people in the U.S. have the implants. For many, CIs achieve near-perfect speech comprehension in ideal listening situations. For others, CIs work less well, and adjustments require lengthy appointments. This project aims to optimize CI configuration by recording neural impulses while the patient is listening to speech. Once neural responses are collected, they may be used to re-program the CI and enhance the implant’s performance, reducing the need for repeated adjustments.
|Drs. Niccolò Terrando and Miles Berger (Anesthesiology), Warren Grill (Biomedical Engineering), Christina Williams (Psychology & Neuroscience), Chay Kuo (Cell Biology), William Wetsel (Psychiatry & Behavioral Sciences)||Bioelectronic Medicine and Cholinergic Regulation of Postoperative Cognitive Dysfunction
Memory dysfunction is a common post-surgical complication and may last for several months, even years. We do not yet know why this decline in memory function occurs, and there is no effective medical treatment to prevent it. The research team has developed a clinically relevant model to study surgery-induced memory dysfunction in mice after a common type of orthopedic surgery. This project will identify cellular processes that may cause post-surgery memory deficits, focusing on interactions between the nervous and immune systems. This work could have a major impact on global health by reducing post-operative cognitive dysfunction.
|Drs. Mohamad Mikati (Pediatrics, Neurobiology), Dwight Koeberl (Pediatrics), Scott Moore (Psychiatry & Behavioral Sciences), William Wetsel (Psychiatry & Behavioral Sciences)||Mechanisms of Increased Hippocampal Excitability in the D801N Knock-in Mouse Model of Na/K ATPase Dysfunction and Rescue with AAV-mediated Gene Therapy
Fifty percent of the energy consumed by brain cells is expended by a cellular pump called the sodium-potassium (chemical symbols: Na/K) ATPase pump. This pump, critical for maintaining the integrity and function of brain cells, is vulnerable to malfunction under stress associated with conditions such as epilepsy and stroke, and others, including Alternating Hemiplegia of Childhood (AHC). AHC is a severe disorder causing paralysis, spasms and epileptic seizures. It is caused by a genetic mutation that codes for a protein in the pump. Using a mouse model with the most common AHC mutation and the disorder, the team will investigate the cell circuitry regulating the pump mechanism. The team will next attempt to use gene therapy to correct the malfunction in the mouse model, which may lead to new therapies for humans with AHC, epilepsy and related conditions.
|Drs. Yiyang Gong (Biomedical Engineering), Jinghao Lu, Fan Wang and Diming Zhang (Neurobiology)||Building a Fiber-Integrated Microscope System for Two-Color Optogenetic Probing of Ensemble Activity in Freely Behaving Animals
Every thought or movement made by our brains requires many neurons. To understand even basic brain function, we must be able to record the activity of many neurons at once. This project will use the techniques of optogenetics and optical engineering to allow researchers to see neurons while they are active. Thus far, this team has developed a mini-microscope that can visualize one type of neurons at a time in awake and moving mice. The next step requires examining multiple types of neurons interacting together.