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2016 Grants - Miller
Optical Tools to Interrogate Neuronal Physiology in Alzheimer’s Disease
Evan Miller, Ph.D.
University of California, Berkeley
2016 New Investigator Research Grant
Can a novel method for measuring electrical activity in nerve cells reveal how cellular communication breaks down in Alzheimer’s disease?
Nerve cells in the brain use electrical signals to communicate with one another across complex networks. These processes are essential for brain function including normal learning and memory. In Alzheimer’s disease, however, electrical activity in the brain can become abnormal and lead to seizures and other harmful events. Such problems may occur, in part, because beta-amyloid protein fragments can hinder the nerve cells’ ability to generate electrical currents. The exact molecular mechanisms of electrical dysfunction in the Alzheimer’s brain have not been identified, in part due to the lack of sensitive tools for recording and measuring electrical activity in nerve cells.
For this research grant, Evan Miller, Ph.D., and colleagues plan to test a novel method for visualizing and measuring changes in nerve cell electrical signals. Their method will involve fluorescent compounds called fluorophores. When expressed in nerve cells, these compounds can visually “highlight” changes in electrical activity through subtle changes in color. The researchers will use color changes to reflect electrical activity changes in nerve cells growing in a laboratory dish — including healthy nerves cells and nerve cells exposed to beta-amyloid. They will determine if beta-amyloid alters nerve cell activity leading to disruption of nerve cell networks. If successful, the research team will begin testing these fluorescent molecules in research animals to determine if they can measure electrical changes in the living brain.
The results of this effort could shed new light on how nerve cell activity becomes abnormal in Alzheimer’s disease and how the disease progresses. This research could also lead to novel methods for diagnosing and treating Alzheimer’s disease at an early stage.