"Place cells" discovered in the rat brain

John O’Keefe
Image: Nobelprize.org
This month John O’Keefe, May-Britt Moser and Edvard Moser were awarded the Nobel Prize in Physiology or Medicine for their work identifying the brain’s “GPS system” – the internal maps that allow us to understand our position in space. The Moser’s discovery of grid cells this century built upon O’Keefe’s earlier accomplishment at UCL in London, the discovery of place cells in the brain. Here, we look back to his 1971 “Short Communication” in the journal Brain Research which presented his preliminary evidence for place cells in rats.

Earlier research had suggested that damage to a rat’s hippocampus (a bilateral brain structure in the temporal lobes) causes it to become confused when attempting spatial tasks. O’Keefe wanted to look in detail at what different hippocampal regions were up to when a rat moves around, specifically to see whether there was a neural system “which provides the animal with a cognitive, or spatial, map of its environment”.

Together with student Jonathan Dostrovsky, O’Keefe inserted microelectrodes through the skulls of 23 rats, each arriving at a slightly different position in the hippocampus. Each rat could then explore its limited environment – a 24cm by 36cm platform – while the experimenters recorded neural activity from the electrodes.

In all, the study took recordings from 76 different positions in the hippocampus. Some turned out to fire in response to particular behaviours, such as walking, eating, or grooming; some while the rat was aware of something; some during sleep; some for no detectable reason at all. But electrodes at eight locations only gave their full response “when the rat was situated in a particular part of the testing platform facing in a particular direction” (italics in original). This was the first ever discovery that different brain cells represent unique location and orientation information.

O’Keefe and Dostrovsky attempted to find straightforward explanations for this spatial sensitivity. But eliminating sound cues (by silencing fans and other unmoving sound sources) and olfactory ones (by rotating the testing platform) had no effect on the neural activity of these eight “place cells*”. This solidified the possibility that the eight weren’t responding to information arriving through the senses from “out there”, but from a representation of space that existed within the brain.

Our findings “suggest that the hippocampus provides the rest of the brain with a spatial reference map,” concluded O’Keefe and Dostrovsky. As explained by Hugo Spiers in next month’s Psychologist magazine, this evidence opened up investigations into spatial memory and cognition, which began to demand some kind of coordinate system feeding into the place cells themselves. That idea was finally cashed out by the Mosers, who established that the entorhinal cortex, a key interface between the hippocampus and the neocortex, contains grid cells that perform this function by encoding atop space grids of hexagons in a honeycomb fashion familiar to anyone who has played too many wargames.

A systematic investigation into the through-lines between neural activity, cognition and behaviour, the body of work by O’Keefe and the Mosers is groundbreaking, genuinely surprising, and provides fertile ground for continued exploration, not only of rats, but of ourselves: minds within bodies within space.
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ResearchBlogging.orgO’Keefe, J., Dostrovsky, J. (1971). The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat Brain Research, 34 (1), 171-175 DOI: 10.1016/0006-8993(71)90358-1

*note the term “place cell” was not used in this paper.

Post written by Alex Fradera (@alexfradera) for the BPS Research Digest.

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