Decoding Memory in Health and Alzheimer’s Disease

Abstract

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.