PROJECT SUMMARY The hippocampus is a brain structure that is critical for normal learning and memory functions. One of the first brain regions to deteriorate in Alzheimer's Disease is the hippocampal memory system, causing the memory deficits that are among the first cognitive symptoms of the disease. To understand why hippocampal damage causes such severe memory deficits, it is necessary to understand the basic computational functions of this brain region. Much research on the hippocampus is derived from the dorsal part of the hippocampus of rodents, whereas the largest part of the hippocampus in humans (i.e., the anterior hippocampus) corresponds to the much-less studied ventral hippocampus in rodents. The ventral hippocampus subserves different behavioral and cognitive functions than the dorsal hippocampus, in large part because the dorsal and ventral parts of the hippocampus are connected to different brain regions. The specific aims of this project are to test the hypothesis that that the dorsal, middle, and ventral parts of the hippocampus, although distinct in their behavioral functions, share a common computational function that is performed on the varying types of input representations received along this axis. Aim 1 will test the specific hypothesis that the computational gradient of spatial pattern separation to pattern completion in the dorsal CA3 region is preserved across all levels of the hippocampal dorsal-ventral axis. To generalize these results to cognitive functions more associated with the ventral hippocampus, Aim 2 will test the hypotheses that (a) proximal CA3 performs a pattern separation function on contextual and odor inputs, whereas distal CA3 performs a pattern completion/generalization function on these inputs, and (b) this gradient is preserved across all levels of the dorsal-ventral axis. Finally, to understand the nature of the inputs from the entorhinal cortex to the hippocampus along the dorsal-ventral axis, Aim 3 will test the hypothesis that the allocentric spatial properties of the medial entorhinal cortex, and the egocentric spatial properties of the lateral entorhinal cortex, are differentially controlled by local and global frames of reference in regions that project to the dorsal hippocampus and the ventral hippocampus, respectively. The results of these experiments will provide crucial knowledge about how the hippocampus performs its mnemonic computations that support our abilities to remember the episodic experiences of our daily lives, including their spatial, social, and emotional contents.