How Place Cells Will Change Neuroscience As We Know It

Neuroscience is the fastest developing field in medicine.  It seems as though everyday there is a new discovery about how, or why our brains work the way they do. On Monday, October 6, the Nobel Prize for Medicine was announced. Researchers John O´Keefe, May-Britt Moser and Edvard I. Moser were awarded the prize jointly for their combined efforts in identifying how the brain understands and processes information about location. Their discoveries open many doors for future Alzheimer’s research and for researchers eager to exploit the brain’s spatial mapping for anti-nausea drugs. However, to understand how these fields will utilize the research, we first must understand the original research.

In 1971, Dr. John O’Keefe published a paper titled “The hippocampus as a spatial map. Preliminary evidence from unit activity in the freely-moving rat.” This title may seem nondescript, but it utilized novel methods to study the brains of moving subjects. Rats were anesthetized before having a microdrive assembly placed upon their heads. Reaching through the skull and into the upper layers of the cortex of the rat, the assembly was able to measure the electrical impulses inside the rat’s brain as it moved around freely. This research was soon followed up by another study in 1976. O’Keefe had identified areas in the rat’s brain that he called “place units,” which he defined as placeswhere the rat’s position on the maze was a necessary condition for maximal cell firing. Some of these place units fired maximally when the animal sniffed in a certain area, either because it found something new there or failed to find something that was usually there. Displace units increased their rates during behaviors associated with theta activity, strong oscillations in brain waves, in the hippocampal slow waves. In general these were behaviors that changed the rat’s position relative to the environment. The results are interpreted as strong support for the cognitive map theory of hippocampal function. The “cognitive map theory” stated that the brain created its own map from which it was able to place the body.

After these early discoveries of “place units” in a mammalian brain, May-Britt Moser and Edvard I. Moser followed up by researching how information is represented in the interface between the hippocampus and the neocortex, part of the cerebral cortex. This area is known as the entorhinal cortex, and it contains billions of entorhinal neurons. After several trials, it was determined that near the postrhinal-entorhinal border, entorhinal neurons had discrete place fields. They were predicting the rat’s location as accurately as place cells in the hippocampus. This discovery confirmed that the human brain creates a directionally oriented, topographically organized neural map of the spatial environment in the dorsocaudal medial entorhinal cortex (dMEC). In other words, the human brain tracked direction, height, and placement simultaneously in the same cells. This neural map uses a type of cell the research duo dubbed “grid cells.” These cells are activated whenever the animal’s position in space coincided with vertexes of a regular grid of triangles spanning the surface of the environment the rat was placed in. This grid creates a hexagonal pattern. This research, however, begged the question of whether information about location, direction and distance is integrated into this complex neural map and how. This time, the researchers focused their efforts on the medial entorhinal cortex (MEC). They recorded from each principal cell layer of MEC in rats that explored two-dimensional environments. These two dimensional environments were often mazes or just an open floor. They found that grid cells were changed by head direction cells, meaning that direction and speed did indeed affect the brain’s neural map. The combination of positional, directional, and translational information in a single MEC cell type enables grid coordinates to be updated during navigation just like a GPS.

The discovery of real time updating neural maps in mammalian brains opens up many possibilities for the future. One of the brightest fields of research lies in cures for Alzheimer’s. Problems with spatial memory and navigation are known to be early indicators of Alzheimer’s disease, a deadly neurological disease that leads to memory loss and death. Researchers compared patients with Alzheimer’s and those without any neurological impairment and found that patients with Alzheimer’s were significantly more likely to get lost. These demonstrations showed that misfiring place cells are early and regular indicators of Alzheimer’s disease. Place cells can be used not only for early diagnosis, but also as a target for next generation drugs and therapies.

Another one of the exciting possibilities for place cells research is in lessening the effects of Post-Traumatic Stress Disorder (PTSD). A group of researchers has recently succeeded in changing the memories associated with certain areas from positive to negative. Even though these experiments were done in rats, these results are immediately applicable to human patients who suffer from place-related PTSD.

Additionally, place cells may hold importance in the study of aging. It has been observed that the function of place cells changes with age. Older rats are less likely to remember paths they have learned recently and are less likely to learn them in the first place. It has also been observed that younger rats have a “plasticity” in their place fields that senile rats do not. When running along a path, younger rats are able to strengthen the links between place cells and allow for faster firing when the route is traversed again. Work has been done to attempt to restore some sort of place-field plasticity to aged rats. Different drugs have been developed that target neurogenesis, the creation of new neurons. However, these drugs have had mixed results, sometimes becoming detrimental when too many neurons are produced.

Scientists across the world are slowly solving the mystery that is place cells. The recent Nobel prizes will add publicity to this already exciting field of research. From Alzheimer’s drugs to PTSD treatment to reversing the effects of aging, place cells hold promise as a way to make some of the most debilitating and inevitable illnesses a thing of the past.

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