Dismantling the Brain’s “GPS” Might Help Understanding Alzheimer’s Disease

In patients suffering from Alzheimer’s disease or dealing with the aftermath of a stroke, a lack of orientation — as if their inner perception of the world in which they always lived in just disappeared — is common. Researchers from the University of California, San Diego School of Medicine induced a version of this loss of orientation in rats and observed important clues to the mystery of why strokes and Alzheimer’s disease can really destroy the sense of direction. The study was published as one of the Cell Reports.

Grid cells and other specific nerve cells placed in the brain are known as “place cells.” Together, they make a sort of “brain’s inner GPS,” as noted in a recent press release. This discovery by John O’Keefe, PhD, director of the Sainsbury Wellcome Centre in Neural Circuits and Behavior at University College London in the United Kingdom, and May-Britt Moser, PhD and her husband Edvard Moser, PhD, both professors of neuroscience at the Norwegian University of Science and Technology in Trondheim. The team was recently awarded with the 2014 Nobel Prize in physiology or medicine.

In that Nobel Prize-awarding research, scientists developed a micro-surgical procedure that allows the removal of the rat’s brain area containing those grid cells. Researchers observed what happened to the rats’ navigational system when those cells were not there. Results showed that they became very poor at doing tasks that depended on their inner skills of orientation.

“Their loss of spatial memory formation was not a surprise (…) It’s what would be expected based on the physiological characteristics of that area of the brain,” confirmed Robert Clark, PhD, a professor of psychiatry also involved in the study. That region is also the first brain area to break down in Alzheimer’s disease cases.

Surprisingly, rats kept another memory and navigation-related set of skills that researchers did not think they would keep without the grid cells. “The surprise is the discovery of the type of memory formation that was not disrupted by the removal of the grid cell area,” Clark noted. Rats noticed a familiar object, and if an object was moved in an environment they knew, they recognized objects and they remembered if they had seen it before. According to the study, electrical signals were transmitted from the hippocampus, pointing to the fact that animals develop place cells that give a sense of location and allow them to know they are passing by a familiar place.

“Their place cells were less precise and less stable, but they were present and active (…) That was a surprise because we had removed the spatially modulated grid-cell input to these neurons,” said Robert Clark. It was assumed that without grid cells projecting its axons into the hippocampus place cells would not be able to develop but that assumption was wrong. “Our work shows a crisp division of labor within memory circuits of the brain (…) Removing the grid-cell network removes memory for places but leaves completely intact a whole host of other important memory abilities like recognition memory and memory of fearful events.”