The ’place cells’, something like our brain GPS

What are place cells and what is their function in our nervous system?

Orientation and exploration in new or unfamiliar spaces is one of the cognitive faculties we use most often. We use it to orient ourselves in our home, our neighborhood, to go to work.

We also rely on it when we travel to a new and unfamiliar city. We even use it when we drive and, possibly, the reader will have been the victim of a careless mistake in his or her orientation or that of a colleague.The 'place cells', something like our brain GPS

What are place cells and what is their function in our nervous system?

Orientation and exploration in new or unfamiliar spaces is one of the cognitive faculties we use most often. We use it to orient ourselves in our home, our neighborhood, to go to work. We also rely on it when we travel to a new and unfamiliar city. We even use it when we drive and, possibly, the reader will have been the victim of an oversight in his or her orientation or that of a colleague, which will have condemned him or her to get lost and forced to drive around in the car until he or she found the right route.It is not the fault of the orientation, it is the fault of the hippocampus. All these are situations that usually frustrate us a lot and lead us to curse our orientation or that of others with insults, shouting and various behaviors. Well, today I will take a look at the neurophysiological mechanisms of orientation.

in our

cerebral GPS

to understand each other.

Let's start by being specific: we should not curse orientation since it is only a product of our neural activity in specific regions. Therefore, we will start by cursing our hippocampus.

The hippocampus as a brain structure

Evolutionarily, the hippocampus is an ancient structure, it is part of the archicortex, that is, those structures that are phylogenetically older in our species. Anatomically, it is part of the limbic system, which also includes other structures such as the amygdala. The limbic system is considered the morphological substrate of memory, emotions, learning and motivation.

The reader, if he is familiar with psychology, will probably know that the hippocampus is a necessary structure for the consolidation of declarative memories, that is, those memories with episodic content about our experiences or semantic content (Nadel and O'Keefe, 1972). Proof of this are the abundant studies that exist about the popular case of "patient HM", a patient who had both temporal hemispheres removed, producing a devastating anterograde amnesia, i.e., he could not memorize new facts although he retained most of his memories from before the operation. For those who want to go deeper into this case, I recommend the studies of Scoville and Millner (1957) who studied the MH patient exhaustively.Place Cells: what are they?

So far we are not saying anything new, nor anything surprising. But it was in 1971 when by chance a fact was discovered that generated the beginning of the study of navigation systems in the brain. O'keefe and John Dostrovski, using intracranial electrodes,

were able to record the activity of specific hippocampal neurons in rats. . This offered the possibility that while performing different behavioral tests, the animal was awake, conscious and moving freely.What they did not expect to discover was that there were neurons that responded selectively depending on the area in which the rat was located. It is not that there were specific neurons for each position (there is no neuron for your bathroom, for example), but that they observed in the CA1 (a specific region of the hippocampus) cells that marked landmarks that could adapt to different spaces.

These cells were called

place cells

. Thus, it is not that there is a place neuron for each particular space you frequent, but rather they are landmarks that relate you to your environment; thus egocentric navigation systems are formed. Place neurons will also form allocentric navigation systems that relate elements of space to each other. Innate programming vs. experience.

This discovery puzzled many neuroscientists, who considered the hippocampus as a declarative learning structure and now saw how it was able to encode spatial information. This gave rise to the "cognitive map" hypothesis, which postulated that a representation of our environment would be generated in the hippocampus.

Just as the brain is an excellent map generator for other sensory modalities such as the coding of visual, auditory and somatosensory signals, it is not unreasonable to think of the hippocampus as a structure that generates maps of our environment and ensures our orientation in them;

it is not unreasonable to think of the hippocampus as a structure that generates maps of our environment and ensures our orientation within them.

Research has gone further and tested this paradigm in very diverse situations. It has been seen, for example, that place cells in maze tasks fire when the animal makes mistakes or when it is in a position where the neuron would habitually fire (O'keefe and Speakman, 1987). In tasks in which the animal must move through different spaces, it has been shown that place neurons fire as a function of where the animal is coming from and where it is going (Frank et al., 2000). How spatial maps are formedAnother major focus of research interest in this area has been on how these spatial maps are formed. On the one hand we could think that place cells establish their function based on the experience we receive when we explore an environment, or we could think that it is an underlying component of our brain circuits, i.e., innate. The question is not yet clear and we can find empirical evidence to support both hypotheses.

On the one hand the experiments of Monaco and Abbott (2014), which recorded the activity of a large number of place cells, have seen that when an animal is placed in a new environment it takes several minutes before these cells start firing normally. Thus,

place maps would be expressed, in a sense, from the moment an animal enters a new environment, but experience would modify these place maps. but experience would modify these maps in the future. Therefore, we could think that brain plasticity is playing a role in the formation of spatial maps. Then, if plasticity really played a role, we would expect that NMDA glutamate receptor knockout mice -that is, mice that do not express this receptor- would not generate spatial maps because this receptor plays a fundamental role in brain plasticity and learning.

Plasticity plays an important role in the maintenance of spatial maps. .

However, this is not the case, and it has been shown that NMDA receptor knockout mice or mice that have been pharmacologically treated to block this receptor express similar patterns of place cell response in novel or familiar environments. This suggests that the expression of spatial maps is independent of brain plasticity (Kentrol et al., 1998). These results would support the hypothesis that navigation systems are independent of learning.

Nevertheless, using logic, brain plasticity mechanisms must clearly be necessary for the memory stability of newly formed maps. And, if this were not the case, what would be the use of the experience that one forms by walking the streets of one's city? Wouldn't we always have the feeling that it is the first time we enter our house? I believe that, as in so many other occasions, the hypotheses are more complementary than they seem and, somehow, in spite of an innate functioning of these functions, plasticity must play a role in maintaining these spatial maps in memory,

plasticity must play a role in the maintenance of these spatial maps in memory. Network, direction and edge cellsIt is rather abstract to talk about place cells, and more than one reader may have been surprised that the same brain area that generates memories serves, so to speak, as a GPS. But we are not done yet and the best is yet to come. Now we're going to really take it up a notch. Initially, it was thought that spatial navigation would depend exclusively on the hippocampus when it was seen that adjacent structures such as the entorhinal cortex showed very weak activation as a function of space (Frank et al., 2000).

However, in these studies activity was recorded in ventral areas of the entorhinal cortex and in later studies dorsal areas were recorded which have a greater number of connections to the hippocampus (Fyhn et al., 2004). Thus, it was observed that many cells in this region

many cells in this region were observed to fire in a position-dependent manner, similar to the hippocampus.

. So far these are results that they expected to find, but when they decided to increase the area to be recorded in the entorhinal cortex, they had a surprise: among the groups of neurons that were activated according to the space occupied by the animal, there were apparently silent areas -that is, they were not activated-. When the regions that did show activation were virtually joined, patterns in the form of hexagons or triangles were observed. They called these neurons in the entorhinal cortex "network cells." By discovering network cells, they saw a possibility of solving the question of how place cells are formed. Since the place cells have numerous connections to the network cells, it is not unreasonable to think that they are formed from these. However, once again, things are not that simple and experimental evidence has not confirmed this hypothesis. The geometric patterns that form the network cells have not yet been interpreted either..

Navigation systems are not limited to the hippocampus.

The complexity does not end here. Even less so when it has been shown that navigation systems are not confined to the hippocampus. This has pushed the boundaries of research to other brain areas, thus discovering other types of cells related to place cells:

direction cells and border cells

Direction cells would encode the direction in which the subject moves and would be located in the dorsal tegmental nucleus of the brainstem. On the other hand, border cells are cells that would increase their firing rate as the subject approaches the limits of a given space and can be found in the subiculum -a specific region of the hippocampus-. We are going to offer a simplified example in which we will try to summarize the function of each cell type: Imagine you are in the dining room of your house and you wish to go to the kitchen. As you are in the dining room of your house, you will have a place cell that will fire as long as you stay in the dining room, but as you want to go to the kitchen you will also have another place cell activated that represents the kitchen. The activation will be clear because your house is a space that you know perfectly well and the activation can be detected in the place cells as well as in the network cells.Now, start walking towards the kitchen. There will be a group of specific direction cells that will now be firing and they will not change as long as you maintain a specific direction. Now, imagine that to go to the kitchen you must turn right and cross a narrow hallway. The moment you turn, your steering cells will know it and another set of steering cells will register the direction it has now taken by activating, and the previous ones will deactivate.

Imagine also that the corridor is narrow and any false move can cause you to hit the wall, so your edge cells will increase their firing rate. The closer you get to the corridor wall, the higher the firing rate your edge cells will show. Think of edge cells like the sensors that some new cars have that make an audible signal when you are maneuvering to park. Edge cells

work similarly to these sensors, the closer they are to colliding the more noise they make. . When you get to the kitchen, your place cells will have told you that it has arrived satisfactorily and because it is a larger environment, your edge cells will relax.Let's finish complicating everything It is curious to think that our brain has ways to know our position. But a question remains: How do we reconcile declarative memory with spatial navigation in the hippocampus, i.e., how do our memories influence these maps? Or could it be that our memories are formed from these maps? To try to answer this question we must think a little further. Other studies have suggested that the same cells that encode space, which we have already discussed, also encode time.

. Thus, there has been talk of time cells (Eichenbaum, 2014) which would encode the perception of time.

The surprising thing is that

there is increasing evidence to support the idea that place cells are the same as time cells. . Therefore, the same neuron, by means of the same electrical impulses, is capable of encoding space and time. The relationship of time and space coding in the same action potentials and their importance in memory remains a mystery.In conclusion: my personal opinion

My opinion on the matter? Taking off my scientist's coat, I can say that human beings are accustomed to think in the easy option and we like to think that the brain speaks the same language as us.. The problem is that the brain offers us a simplified version of reality that it processes itself. In a way similar to the shadows in Plato's cave. So, just as in quantum physics we break down the barriers of what we understand as reality, in neuroscience we discover that in the brain things are different from the world that we perceive consciously and we must be very open-minded to the fact that things do not have to be as we really perceive them.

The only thing that is clear to me is something that Antonio Damasio often repeats in his books:

the brain is a great generator of maps . Perhaps the brain interprets time and space in the same way to form maps of our memories. And if it seems chimerical to you, think that Einsten in his theory of relativity, one of the theories he postulated was that time could not be understood without space, and vice versa. Unraveling these mysteries is undoubtedly a challenge, even more so when they are difficult to study in animals. However, no effort should be spared in these matters. First of all, out of curiosity. If we study the expansion of the universe or the recently recorded gravitational waves, why shouldn't we study how our brain interprets time and space? Secondly, many neurodegenerative pathologies such as Alzheimer's disease have spatiotemporal disorientation as their first symptoms. Knowing the neurophysiological mechanisms of this coding, we could discover new aspects that would help to better understand the pathological course of these diseases and, who knows, discover new pharmacological or non-pharmacological targets.

•  
• Bibliographic references:
•  
• Eichenbaum H. 2014. Time cells in the hippocampus: a new dimension for mapping memories. Nature 15: 732-742
• Frank LM, Brown EN, Wilson M. 2000. Trajectory encoding in the hippocampus and entorhinal cortex. Neuron 27: 169-178.
• Fyhn M, Molden S, Witter MP, Moser EI, Moser M-B. 2004. Spatial representation in the entorhinal cortex. Science 305: 1258–1264
• Kentros C, Hargreaves E, Hawkins RD, Kandel ER, Shapiro M, Muller RV. 1998. Abolition of long-term stability of new hippocampal place cell maps by NMDA receptor blockade. Science 280: 2121–2126.