"Decoding Memory in Health and Alzheimer’s Disease"
Annabelle Singer, Ph.D.
Wallace H. Coulter Department of Biomedical Engineering
Georgia Tech and Emory University
In this talk I will discuss how neural activity goes awry in Alzheimer’s disease, driving specific frequencies of neural activity recruits the brain’s immune system, and new methods to drive rhythmic activity non-invasively. Spatial navigation deficits are one of the earliest symptoms of AD and the hippocampus is one of the areas first affected by the disease. First, I will describe how neural codes underlying memory-based spatial decisions fail in animal models Alzheimer’s disease (AD). Using a virtual reality behavior paradigm to record and manipulate neural activity in transgenic mice, the primary animal model of AD, we found deficits in hippocampal neural activity early in the progression of the disease. These deficits occurred in the same patterns of activity that we have found inform memory-guided decisions in a spatial navigation task. Next, I will discuss the effects of driving these patterns of activity in AD model mice. We found that driving gamma activity, the activity lacking in AD mice, mobilized the immune system to remove pathogenic proteins. Specifically, driving gamma recruited the primary immune cells of the brain, microglia, to alter their morphology and increase engulfment of beta-amyloid. Finally, I will discuss new non-invasive methods we are developing to drive rhythmic neural activity non-invasively. Ultimately, these discoveries could lead to new therapies for Alzheimer’s disease by driving specific patterns of neural activity to impact the disease at the cognitive, cellular, and molecular levels.
Annabelle Singer is a neuroscientist with extensive experience in the biology of learning and memory from health to disease, from animal models to humans, and from computations within neurons to across populations of cells. She is currently an Assistant Professor in George Tech’s Department of Biomedical Engineering. She completed a post-doctoral fellowship in Ed Boyden’s Synthetic Neurobiology Group at MIT and she received her Ph.D. in Neuroscience from UCSF, performing research in the laboratory of Loren Frank. Singer’s long-term goal is to understand how neural activity produces memories and protects brain health. Using this knowledge, she is engineering neural activity to treat brain diseases. To achieve these aims, Singer integrates innovative engineering, biology, and computational approaches toexamine how coordinated electrical activity across many neurons represents memories of experiences and how this activity fails in disease. Singer’s discoveries have resulted in a series of first author peer-reviewed papers, dozens of talks and presentations, and both popular science articles and academic commentary. In the course of her research Singer has developed new methods to simultaneously record neural inputs and outputs during behavior in awake behaving animals, new approaches to analyze complex neural data, and new therapeutic approaches to treat cognitive disease.