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The article comments on reports within the issue by researchers M. M. Yartsev and colleagues and J. G. Heys and team on the perception and neural coding of three-dimensional (3D) space in mammal brains, with particular focus on the mapping of place cell neurons in the hippocampus and grid cells in the medial entorhinal cortex. Yartsev and team looked at brain theta wave activity and 3D space encoding of hippocampal neurons of bats in flight. Heys and team compared theta rhythms of medial entorhinal cortex grid cells of bats and rats related to space coding.

Alzheimer's disease (AD) manifests with memory loss and spatial disorientation. AD pathology starts in the entorhinal cortex, making it likely that local neural correlates of spatial navigation, particularly grid cells, are impaired. Grid-cell-like representations in humans can be measured using functional magnetic resonance imaging. We found that young adults at genetic risk for AD (APOE-ε4 carriers) exhibit reduced grid-cell-like representations and altered navigational behavior in a virtual arena. Both changes were associated with impaired spatial memory performance. Reduced grid-cell-like representations were also related to increased hippocampal activity, potentially reflecting compensatory mechanisms that prevent overt spatial memory impairment in APOE-ε4 carriers. Our results provide evidence of behaviorally relevant entorhinal dysfunction in humans at genetic risk for AD, decades before potential disease onset., (Copyright © 2015, American Association for the Advancement of Science.)