Hippocampal Codes in Spatial Memory and Alzheimer’s Disease

Abstract

The hippocampus is essential for both spatial navigation and episodic memory. While decades of research has revealed patterns of neural activity in the hippocampus that represent information about the spatial environment, called spatial coding, how these patterns relate to memory processes is still unclear. Our lab uses a combination of behavior, neural recording, optogenetic manipulation, and computational tools to understand the neural underpinning of learning and memory in health and disease. In this talk I will address how hippocampal neural codes guide memory-based decisions and how they go awry in disease’s that effect memory. First, by recording the activity of many single neurons simultaneously as an animal learns a spatial navigation task, we examined how spatial codes inform future decisions. We found that when an animal has to choose a path through space, the hippocampus reactivates neural activity that represents the possible paths to choose from, essentially foreseeing where to go based on past experience. We then examined how this activity fails in Alzheimer’s disease (AD), since spatial navigation deficits are one of the earliest symptoms of AD and the hippocampus is one of the areas first affected by the disease. 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. Finally, I will discuss optogenetically driving these patterns of activity in the AD mouse model.