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How You Know Where You Are


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April 5, 2013

A sense of place—knowing where you are—exists in our minds almost without thought; scientists believe the knowledge arises within so-called place cells, neurons in the hippocampus that fire whenever an animal is in a particular location.

How the place cells actually compute and determine spatial location is not well understood. But using a technique that combines electrophysiology and optogenetics, researchers in Norway have now illuminated an array of neurons that feed the place cells.

“The technique is used for the first time to investigate how signals emerge in a cortical brain circuit,” said Edvard Moser, director of the Kavli Institute for Systems Neuroscience at the Norwegian University of Science and Technology and author of a study published in Science yesterday that reports the findings. “The cortex is where the most advanced cognition takes place. So this is a very valuable tool.”

In 2005, Moser and his wife and collaborator May-Britt Moser stunned the field of neuroscience with their discovery that neurons called grid cells in the entorhinal cortex of the brain create mental maps and superimpose them on the world. When a rat wanders within a space, these grid cells fire periodically. When the periodic firings of each cell are overlaid with the rat’s wanderings, amazingly, a grid of perfect equilateral triangles emerges—a tesselation that allows the animal to relate one area to another, like latitude and longitude coordinates on the Earth.

Researchers assumed that these grid cells send axons into the hippocampus, connecting with place cells. But what remained unclear was the percentage of grid cells that connect to place cells, whether other types of neurons also play a role in spatial cognition, and just what the entire circuit looks like.

To figure this out, Moser’s team decided to exploit recent advances in optogenetics that allow researchers to control the firing of neurons with light.

First, the team inserted a gene called Channelrhodopsin-2 (ChR2) that encodes a light-sensitive ion channel into a recombinant adeno-associated virus. The researchers then injected that adenovirus into the hippocampus of rats where the gene was taken up and expressed by the neurons whose axons project into the hippocampus.

By shining a light into the rats’ hippocampuses, Moser and colleagues traced the axons expressing ChR2 back to the entorhinal cortex and conducted electrophysiological recordings on individual neurons, all while the rat freely wandered.

Moser and his team found that, while about a quarter of place cell connectors were grid cells, many were other types of spatial cells. And surprisingly, more than half of these place cell connectors were non-spatial cells.

Moser says work like this can aid our understanding of Alzheimer’s disease, since these cells are in an area of the brain that’s among the first to be damaged by Alzheimer’s neurodegeneration. But, he says, knowing how the brain computes and visualizes space is fascinating all by itself.

“The place cells and grid cells are very accessible signals, you can really measure them. There’s no doubt when you have such a cell, and that is quite unique in the cortex,” he says. “They are a window into how the cortex is operating.”


Zhang, S.-J., J. Ye, C. Miao, A. Tsao, I. Cerniauskas, D. Ledergerber, M.-B. Moser, and E. I. Moser. 2013. Optogenetic dissection of Entorhinal-Hippocampal functional connectivity. Science 340(6128).

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