Project Summary / Abstract Our brain provides us with a sense of where we are in space. The importance of this sense is clear when we become spatially disoriented, like when one is confused about one’s orientation after exiting a subway station. Central to the understanding of how brains give rise to spatial cognition has been the discovery of place cells in the 1970’s (i.e., neurons that are active when animals are in one location in space), head-direction cells in the 1980’s (i.e., neurons that are active when animals face one compass direction), and grid cells in the early 2000’s (i.e., neurons that are active when animals are in a grid of locations in space). A fundamental next step in our understanding of spatial cognition would be to describe the circuit-level interactions that give rise to such physiological activity patterns and to understand how such signals ultimately influence navigational behavior. We wish to leverage the advanced genetic, behavioral, anatomical and physiological tools in Drosophila, to achieve three broad goals. First, we wish to rigorously characterize neural circuits that explain how navigational signals are built. Second, we wish to improve the tasks that flies perform while we record from their brain, which will allow us to isolate cells and circuits required for the formation of spatial working memories. Third, we aim to reveal molecular, cellular and circuit mechanisms by which such memories are formed and guide behavior. This work should allow us to more rigorously link molecular factors, through their effects on cells and circuits, to their function in spatial-cognition. Our discoveries should ultimately help to inform how humans perform navigational tasks like driving home from work or finding a car in a parking lot, alongside how to approach neurological conditions in which such abilities are impaired, like in Alzheimer’s disease.

Project Narrative Several dementias, including Alzheimer’s disease, include deteriorations in our ability to understand and remember where we are in space. A richer cellular and circuit-level understanding of how spatial navigation is achieved may inform novel therapeutic strategies for targeting these conditions, reducing the heavy burden they place on individuals and society.