Retrosplenial Circuits Underlying Landmark Stability

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PROJECT SUMMARY Vision is key to spatial navigation, because visual landmarks guide us through our everyday lives. However, some landmarks become unreliable because they shift their location over time. Recent research suggests an area of the brain known as the retrosplenial cortex processes landmarks and evaluates their stability1. The retrosplenial cortex lies at a nexus between the hippocampal formation—a structure critical for navigation, learning, and memory—and the visual cortex. The anatomical and functional connections have suggested retrosplenial cortex is a site of visuospatial processing for some time2. And in fact, patients with damage to RSC have difficulty utilizing landmarks to navigate through familiar environments, learning new routes, and performing visual memory tasks3. But only recently have “place” cells been discovered in mouse retrosplenial cortex, which encode the animal’s position in the world4. Our preliminary data suggest place cells can be seen while an animal runs through a visual, virtual-reality track. We hypothesized that these place representations may be strongly influenced by the movement of local landmarks, thus encoding both space and landmark stability. This proposal lays out a strategy for testing this hypothesis using in vivo two-photon calcium imaging and immersive virtual reality environments. First the proposal aims to fully characterize the visual properties of retrosplenial “place” cells. Second, the proposal aims to test whether areas of high landmark instability are encoded by fewer place fields. Finally, the proposal focuses on the moment a landmark begins moving to see if the neural circuits show signs of becoming plastic. Scientists have long been interested in how the brain enables spatial navigation. Not only is spatial navigation essential to daily life, but the neural circuits involved overlap significantly with brain regions that process learning and memory. If successful, this study will generate insight into the neural circuits of navigation and the essential contribution of visual landmark processing. These results will add basic knowledge into how these circuits function in health and why they are vulnerable to diseases such as neurodegeneration and stroke. The project will also inform the scientific and medical communities on the proper design of immersive sensory interfaces for behavioral assessment in animals and potentially rehabilitative therapies in humans.