Optical Imaging and Manipulation of Medial Entorhinal Cortex Grid Cells

The ability for animals to perform spatial navigation and remember where resources are located in an environment is necessary for survival. In all mammals, including rodents, bats, non-human primates and humans, a region of the brain known as the medial entorhinal cortex is critically involved in spatial navigation and spatial memory, but it remains unknown how the medial entorhinal cortex is organized to perform these functions. Solving this problem has been limited by our ability to monitor and manipulate the activity of many brain cells simultaneously while animals perform spatial navigation behavior. In order to understand how the medial entorhinal cortex is organized we have designed a novel method that enables simultaneous monitoring and precise manipulation of hundreds of brain cells while a mouse is navigating through a spatial environment. Using this method, the experiments proposed in this application will test a key prediction made by a computational model of medial entorhinal cortex. These results will determine how the medial entorhinal cortex is functionally organized and how this brain region could be used in spatial navigation and spatial memory.