Grid Cell - Background

Background

In 1971, John O'Keefe and Jonathon Dostrovsky reported the discovery of place cells in the rat hippocampus — cells that fire action potentials when an animal passes through a specific small region of space, which is called the place field of the cell. This discovery, although controversial at first, led to a series of investigations that culminated in the 1978 publication of a book by O'Keefe and his colleague Lynn Nadel called The Hippocampus as a Cognitive Map — the book argued that the hippocampal neural network instantiates cognitive maps as hypothesized by the psychologist Edward C. Tolman. This theory aroused a great deal of interest, and motivated hundreds of experimental studies aimed at clarifying the role of the hippocampus in spatial memory and spatial navigation.

Because the entorhinal cortex provides by far the largest input to the hippocampus, it was clearly important to understand the spatial firing properties of entorhinal neurons. The earliest studies, such as Quirk et al. (1992), described neurons in the entorhinal cortex as having relatively large and fuzzy place fields. The Mosers, however, thought it was possible that a different result would be obtained if recordings were made from a different part of the entorhinal cortex. The entorhinal cortex is a strip of tissue running along the back edge of the rat brain from the ventral to the dorsal sides. Anatomical studies had shown that different sectors of the entorhinal cortex project to different levels of the hippocampus: the dorsal end of the EC projects to the dorsal hippocampus, the ventral end to the ventral hippocampus. This was relevant because several studies had shown that place cells in the dorsal hippocampus have considerably sharper place fields than cells from more ventral levels. Every study of entorhinal spatial activity prior to 2004, however, had made use of electrodes implanted near the ventral end of the EC. Accordingly, together with Marianne Fyhn, Sturla Molden and Menno Witter, the Mosers set out to examine spatial firing from the different dorsal-to-ventral levels of the entorhinal cortex. They found that in the dorsal part of medial entorhinal cortex (MEC), cells had sharply defined place fields like in the hippocampus but the cells fired at multiple locations. The arrangement of the firing fields showed hints of regularity, but the size of the environment was too small for spatial periodicity to be visible in this study.

The next set of experiments, reported in 2005, made use of a larger environment, which led to the recognition that the cells were actually firing in a hexagonal grid pattern. The study showed that cells at similar dorsal-to-ventral MEC levels had similar grid spacing and grid orientation but the phase of the grid (the offset of the grid vertices relative to the x and y axes) appeared to be randomly distributed between cells. The periodic firing pattern was expressed independently of the configuration of landmarks, in darkness as well as in the presence of visible landmarks and independently of changes in the animal’s speed and direction, leading the authors to suggest that grid cells expressed a path-integration dependent dynamic computation of the animal’s location.