The 'cells of place', something like our brain GPS

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

We also depend on it when we travel to a city new and unknown to us. We use it even when we drive and, possibly, the reader will have been the victim of a carelessness in the orientation of him or her on some occasion. in that of a colleague, which will have condemned him to get lost, being forced to drive the car around until he found the route adequate.

It's not the orientation's fault, it's the hippocampus's fault

All these are situations that usually frustrate us a lot and that lead us to curse our orientation or that of others with insults, yelling and various behaviors. Well, Well, today I will give a brushstroke on the neurophysiological mechanisms of orientation, in our Brain gps to understand us.

We will start by being specific: we must not curse the orientation since this is only a product of our neuronal activity in specific regions. Therefore, we will begin 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, in which other structures such as the amygdala are also found. The Limbic System is considered the morphological substrate of memory, emotions, learning and motivation.

The reader, possibly if he is used to psychology, will know that the hippocampus is a necessary structure for the consolidation of memories. declarative, that is, with those memories with episodic content about our experiences or semantic (Nadel and O'Keefe, 1972).

Proof of this are the abundant studies that exist about the popular case of the “HM patient”, a patient who had had both temporal hemispheres removed. producing a devastating anterograde amnesia, that is, he could not memorize new facts although he retained most of his memories from before the operation. For those who want to delve into this case, I recommend the studies by Scoville and Millner (1957) who exhaustively studied the HM patient.

The Cells of Place: what are they?

So far we do not say anything new, or 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 behavior tests, the animal was awake, conscious and moving freely.

What they did not expect to discover was that there were neurons that responded selectively based on the area in which the rat was located. It is not that there were specific neurons at each position (there is no neuron for your bathroom, for example), but that observed in CA1 (a specific region of the hippocampus) cells that marked landmarks that could adapt to different spaces.

These cells were called place cells. Therefore, it is not that there is a neuron of place for each specific space that you frequent, but rather they are reference points that relate you to your environment; this is how egocentric navigation systems are formed. The neurons of place will also form allocentric navigation systems that will relate elements of space to each other.

Innate programming vs experience

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

Same as him brain It is an excellent generator of maps 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 that guarantees our orientation in 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 in which the neuron would normally fire (O'keefe and Speakman, 1987). In tasks in which the animal must move through different spaces, it has been seen that place neurons fire depending on where the animal comes from and where it is going (Frank et al., 2000).

How spatial maps are formed

Another of the main focuses 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 might think that it is an underlying component of our brain circuits, that is, innate. The question is not yet clear and we can find empirical evidence that supports both hypotheses.

On the one hand, the experiments of Monaco and Abbott (2014), which recorded the activity of a large number of site cells, have since when an animal is placed in a new environment, it takes several minutes for these cells to start firing with normal. So that, place maps would be expressed, in some way, from the moment an animal enters a new environment, but experience would make these maps modify in the future.

Therefore, we could think that brain plasticity is playing a role in the formation of spatial maps. Then, if plasticity really did play a role, we would expect knockout mice to the NMDA receptor for the neurotransmitter glutamate - that is, mice which do not express this receptor - did not generate spatial maps because this receptor plays a fundamental role in brain plasticity and the learning.

Plasticity plays an important role in maintaining spatial maps

However, this is not the case, and it has been seen that knockout mice to the NMDA receptor or mice that have been treated pharmacologically To block this receptor, they express similar patterns of response from place cells in new 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.

Despite everything, using logic, the mechanisms of brain plasticity must be clearly necessary for the memory stability of newly formed maps. And, if it were not like that, what use would the experience that one forms from walking the streets of their city be? Wouldn't we always have the feeling that it is the first time we have entered our house? I believe that, as on so many other occasions, the hypotheses are more complementary than they seem and, somehow, despite an innate functioning of these functions, plasticity has to play a role in keeping these spatial maps in memory.

Net, address and edge cells

It is quite abstract to talk about cells of place and possibly more than one reader has been surprised that the same brain area that generates memories serves, so to speak, as GPS. But we are not done and the best is yet to come. Now let's curl the curl for real. At first, it was thought that space 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. al., 2000).

However, in these studies, activity was recorded in ventral areas of the entorhinal cortex and in studies posterior areas, dorsal areas were recorded which have a greater number of connections to the hippocampus (Fyhn et al., 2004). So that many cells in this region were observed to fire as a function of position, similar to the hippocampus. So far they are results that were expected to be found, but when they decided to increase the area that they would register in the entorhinal cortex they had a surprise: Among the groups of neurons that were activated as a function of 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, a possibility was seen to solve the question of how cells of place are formed. Since cells have numerous connections of network cells, it is not unreasonable to think that they are formed from these. However, once again, things are not so straightforward and experimental evidence has not confirmed this hypothesis. The geometric patterns that form the network cells have not yet been interpreted.

Navigation systems are not confined to the hippocampus

The complexity does not end here. Even less when it has been seen that navigation systems are not limited to the hippocampus. This has expanded the limits of research to other brain areas, thus discovering other types of cells related to local cells: direction cells and edge cells.

Steering cells would encode the direction in which the subject moves and would be located in the dorsal tegmental nucleus of the brainstem. Edge cells, on the other hand, are cells that would increase their firing rate as the subject becomes approach the limits of a given space and we can find them in the subiculum - specific region of the hippocampus-. We are going to offer a simplified example in which we will try to summarize the function of each type of cell:

Imagine that you are in the dining room of your house and you want to go to the kitchen. Since you are in the dining room of your house, you will have a place cell that will fire as long as you remain in the dining room, but since you want to go to the kitchen you will also have another activated place cell that represents the kitchen. The activation will be clear because your home is a space that you know perfectly well and the activation can be detected both in the place cells and in the network cells.

Now, start walking towards the kitchen. There will be a group of specific address cells that will now be firing and will not change as long as you maintain a specific address. Now, imagine that to go to the kitchen you have to turn right and cross a narrow hallway. The moment you turn, your steering cells will know it and another set of steering cells will record the direction it has now taken turning on, and the previous ones will turn off.

Also imagine that the corridor is narrow and any wrong movement can cause you to hit the wall, so your edge cells will increase their rate of fire. The closer you get to the corridor wall, the higher the firing rate its edge cells would show. Think of edge cells like the sensors some newer cars have that give an audible signal when you're maneuvering to park. Border cells They work in a similar way to these sensors, the closer you are to colliding the more noise they make. When you get to the kitchen, your cells of place will have indicated to you that it has arrived satisfactorily and being a larger environment, your cells of edge will relax.

Let's finish complicating everything

It is curious to think that our brain has ways of knowing our position. But a question remains: How do we reconcile declarative memory with spatial navigation in the hippocampus? That is, how do our memories influence these maps? Or could it be that our memories were formed from these maps? To try to answer this question we must think a little further. Other studies have pointed out that the same cells that encode space, of which we have already spoken, also encode time. Thus, there has been talk of time cells (Eichenbaum, 2014) which would encode the perception of time.

The surprising thing about the case is that there is increasing evidence supporting the idea that cells of place are the same as cells of time. Then, the same neuron through the same electrical impulses is able to encode space and time. The relationship of the encoding of time and space in the same action potentials and their importance in memory remain a mystery.

In conclusion: my personal opinion

My opinion about it? Taking off my scientist gown, I can say that human beings tend to think of 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. Thus, just as in quantum physics barriers are broken of what we understand as reality, in the neuroscience we discover that in the brain things are different from the world we perceive consciously and we must have a very open mind that things do not have to be as they really are we perceive them.

The only thing that is clear to me is something that Antonio Damasio uses to repeat a lot in his books: the brain is a great map generator. 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 that he postulated was that time could not be understood without space, and vice versa. Undoubtedly unraveling these mysteries is a challenge, even more so when they are difficult aspects to study in animals.

However, no effort should be spared on these issues. First 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? And secondly, many of the neurodegenarative pathologies like Alzheimer's disease, their first symptoms are spatio-temporal disorientation. Knowing the neurophysiological mechanisms of this coding we could discover new aspects that will help to better understand the pathological course of these diseases and, who knows, whether to discover new drug targets or not pharmacological.

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.
• Monaco JD, Abbott LF. 2011. Modular realignment of entorhinal grid cell activity as a basis for hippocampal remapping. J Neurosci 31: 9414–9425.
• O'Keefe J, Speakman A. 1987. Single unit activity in the rat hippocampus during a spatial memory task. Exp Brain Res 68: 1 –27.
• Scoville WB, Milner B (1957). Loss of recent memory after bilateral hippocampallesion. J Neurol Neurosurg Psychiatry 20: 11–21.