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The brain contains a unique set of cells that fire in perfect hexagonal spatial arrays. Since these “grid cells” were discovered in rats in 2005, scientists have been trying to figure out what produces this unusual hexagonal firing pattern. They may now be close to an answer: A new study at the Weizmann Institute conclusively shows that one of the two proposed models for grid cell activity does not hold up in a second mammal – the bat – making it unlikely to be valid. The results of this research appeared recently in Nature.
Grid cells are found in a part of the brain called the entorhinal cortex; they are active when the animal roams around a space. In addition, they are thought to communicate with “place cells” in the hippocampus, next door. Grid cells appear to help map the environment by creating a sort of reference grid – firing when the animal crosses a node – while place cells relate to specific locations.
The model tested by Dr. Nachum Ulanovsky and research student Michael Yartsev of the Weizmann Institute’s Neurobiology Department, together with Prof. Menno Witter of the Norwegian University of Science and Technology in Trondheim, Norway, suggested that periodic oscillations in neural activity give rise to the grid pattern. Such regular, wave-like oscillations had been observed in the rat entorhinal cortex simultaneously with grid-cell firing. The supposition was that the oscillation – a periodic pattern in time – is converted by the brain to a periodic pattern in space, i.e., the grid structure.
But does the fact that the two periodicities – spatial and temporal – always occur together mean that one causes the other? In rats, it is impossible to separate them; but Ulanovsky suspected that the bats he studies – Egyptian fruit bats – might not exhibit such a neat correlation. In a previous study of bat place cells, he had noted oscillations that were very different from those of rats, and he hypothesized that this dissimilarity might apply to grid-cell activity, as well.
To find out, the researchers first had to locate the bats’ entorhinal cortex and pinpoint the exact location of the grid cells – a long process undertaken by the Weizmann researchers in collaboration with the Trondheim lab of Witter, a noted expert on brain anatomy. Ulanovsky and Yartsev then carefully inserted tiny electrodes into the area containing grid cells and recorded their activity as the bats crawled around the floor of a box, replicating the rat experiments as closely as possible.
Their findings showed that the bat grid cells fired in a neat hexagonal array nearly identical to that of rats; the similarity extended to the smallest details of the hexagons’ properties. But the oscillations in time were completely different: Instead of regular waves, the bats’ brains revealed short bouts of oscillation interspersed with longer quiescent periods – putting them at odds with the model. Further mathematical analysis showed that the grid patterns remain unchanged even if oscillations are identified and removed from the analysis. In other words, there is no real correlation between the oscillations and the grids; oscillations cannot be the cause of the grid cells’ unique ordered patterns.
By disproving the first model, Ulanovsky and his colleagues have lent strong support to the second, alternative model, which proposes that the pattern arises because the cells work as a network. The hexagonal layout is explained by the fact that a hexagon is the one formation in which all the activity nodes are equidistant, leading to the minimum-energy, most stable pattern of the network model. This principle is seen elsewhere in nature, for instance in honeycombs, in which the hexagon shape provides a strong structure that yields a minimum-energy, stable configuration.
Dr. Nachum Ulanovsky's research is supported by the Nella and Leon Benoziyo Center for Neurological Diseases; the Clore Center for Biological Physics; the Carl and Micaela Einhorn-Dominic Brain Research Institute; the Irving B. Harris Foundation; the estate of Fannie Sherr; Mr. and Mrs. Steven Harowitz, San Francisco, CA; and the European Research Council.
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