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Imagine being home on a moonless night when the power unexpectedly goes out. You are shrouded by silent darkness, instantly blind to your surroundings. Yet despite this sensory deprivation, you can navigate somewhat effortlessly around the futon, through the doorway of the kitchen, and across to the middle drawer where your lighter is stored, avoiding walls, furniture, and other familiar obstacles along the way. How, without vision or echolocation, did you remember where everything was in relation you and to everything else?

The brain's "spatial memory," as this ability is called, relies on the operation of neural "maps." Critical to these maps are specialized neurons known as "place cells," which are located in the hippocampal formation. These cells show place-specific firing patters; that is, a given place cell will become highly activated only when an animal is at a specific location within a particular environment. Theoretically, networks of place cells, each activated in a distinct but partially overlapping spatial region, form maps of every environment encountered. If an environment is experienced repeatedly, the map will be committed to long-term memory; the brain can then deduce its animal's location by interpreting the activation of place cells along the relatively stable map.

Importantly, place cell activation patterns are based on spatial clues. In the introductory example, you could navigate in darkness only because you knew your relative position at the time of the power outage. If, however, you were to close your eyes and twirl around on your toes, and open your eyes immediately after the outage began, your internal map (and thus you), would be spatially bewildered. Yet if you were to grope and fumble until you found the futon, your map would reorient, allowing you to immediately intuit the rest of your spatial world.

What about when two environments have similar spatial cues? For example, imagine two parallel streets in San Francisco, each lined by eminent Victorians, peppered with sushi restaurants, cafes, and liquor stores, a MUNI rail cutting a rugged metallic swath down the middle of each street. The spatial cues of these two environments would activate a somewhat overlapping pattern of place cells, yet the subtle differences on each street (an Indian-Pakistani restaurant on the north side of one, a pirate store on the south side of the other) would allow you to recognize the differences and navigate each uniquely. How does your brain recognize such relatively small differences to construct the distinct maps the environments deserve?

Researchers at the University of Bristol and MIT published a report in the early online edition of Science on June 7 that explored this question. The group focused on the role of a particular region of the hippocampal formation, the dentate gyrus, and found it to be crucial for distinguishing between similar locations. The dentate gyrus does not contain place cells, but it does serve as an interface between the hippocampus (where the place cells are located) and the rest of the brain (which would provide the sensory information, the spatial cues). Thus, it may provide the neural input necessary for "map" construction.

The group removed the NMDA receptor, a protein crucial for synaptic plasticity (the process by which the connection between two neurons adapts to become stronger or weaker, thus enabling learning and memory), specifically from the dentate gyrus. Although these mice perform normally in several learning and memory tasks, they had trouble discriminating between similar yet distinct environments. At the neuronal level, their place cells showed decreased spatial specificity, becoming activated in a significantly broader range.

This type of deficit is similar to what has been previously observed in aged animals; these results may thus help explain the disorientation experienced by some older people, who often struggle to adapt to new spatial locations. Perhaps a major component of their impairment is an age-related dysfunction in the dentate gyrus, which makes it difficult to encode subtle differences and form unique place cell maps for similar yet distinct places. Such individuals would also lose their bearings as a result of changes to familiar environments; e.g., a few years ago I moved some of my grandmother's icons around on her computer's desktop, and she was completely bewildered until I dragged them all back to their original, recognizable locations.

Reference:
McHugh TJ et al. "Dentate gyrus NMDA receptors mediate rapid pattern separation in the hippocampal network" Science. [Published online June 7 2007, DOI: 10.1126/science.1140263]