Entorhinal grid cells and hippocampal memory

More than 30 years of research have pointed to the hippocampus as a key component of the brain's circuit for spatial representation. Although place-specific firing is undoubtedly the most conspicuous behavioural correlate of hippocampal principal neurons, hippocampal neurons also respond to a variety of non-spatial sensory inputs, and they can alternate between multiple representations of the same location, suggesting that the spatial signal itself originates from outside the hippocampus. We have shown th at the medial entorhinal cortex, one synapse upstream of the hippocampus, contains a metric representation of current location. Self-location is represented in this area by a network of spatially tuned grid cells, whose firing locations form a periodic tr iangular pattern tiling the entire environment of the animal, resembling the cross points of graph paper except that the unit is triangular and not square. Grid cells have a number of properties implying them as part of the brain's coordinate system for s elf-motion based metric calculation. The aim of this proposal is to establish the organization of the microcircuit by which spatial location is computed from directional and distance-related inputs within the microcircuit of diverse cell types in the medi al entorhinal cortex, and to determine how spatial representations in entorhinal grid cells interact with cells in other cortical brain regions such as the hippocampus. The representation of spatial location has appeared as one of the first cognitive func tions to be understood in mechanistic detail, and we shall to use the opportunities emerging from our recent discoveries to understand general principles of computation in cortical microcircuits. The results will ultimately benefit the development of tool s for the diagnosis and treatment of Alzheimer's disease, which commonly begins in just the brain area that contains the grid cells.