The “ place cells ”, a kind of GPS of our brain

Orientation and exploration in new or unfamiliar spaces is one of the cognitive skills 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 go to a new city that is unknown to us. It is even used while driving and, eventually, the reader will have at some point been the victim of a recklessness in his orientation or that of a colleague, which will have condemned him to lose sight of it. He is forced to turn the car around until he finds the right route.

It’s not the fault of the orientation, it’s the fault of the hippocampus

These are all situations that often frustrate us a little and lead us to curse our own orientation or that of others with insults, yelling and various behaviors. good because today I am going to give a brushstroke on the neurophysiological mechanisms of orientation, In our brain GPS to understand us.

We’ll start off by being specific: we shouldn’t curse orientation as it’s just a product of our neural activity in specific regions. So let’s start by cursing our seahorse.

The hippocampus as a brain structure

Evolutionarily, the hippocampus is an ancient structure, 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 like the amygdala are also found. The limbic system is considered to be the morphological substrate of memory, emotions, learning and motivation.

The reader can know if he is used to psychology that the hippocampus is a necessary structure for the consolidation of declarative memories, that is to say with those memories with episodic content on our experiences or semantics (Nadel and O ‘ Keefe, 1972).

Proof of this are the many studies that exist on the popular case of the “patient HM”, a patient whose two temporal hemispheres had been removed, producing devastating anterograde amnesia, meaning he could not memorize. his memories before the operation. For those who want to dig deeper into this case, I recommend the studies by Scoville and Millner (1957) who exhaustively studied the HM patient.

Place cells: what are they?

So far, we’re not saying anything new, or anything surprising. But it was in 1971 that by chance a fact was discovered which led to the start of the study of navigation systems in the brain. O’Keefe and John Dostrovski, using intracranial electrodes, they were able to record the activity of specific hippocampal neurons in rats. This offered the possibility that by performing different behavioral tests, the animal would be awake, conscious and move freely.

What they didn’t expect to find was that there were neurons that responded selectively based on the area the rat was in. It’s not that specific neurons existed at each position (there is no neuron for their bathroom, for example), but that cells were tagged in CA1 (a specific region of the hippocampus). which marked reference points that could be adapted to different spaces.

These cells were called place cells. So it’s not that there is a place neuron for each particular space you frequent, but rather landmarks that connect you to your surroundings; this is how self-centered navigation systems are formed. The place neurons will also form allocentric navigation systems that will connect the elements of space to each other.

Innate programming vs experience

This discovery intrigued many neuroscientists, who viewed 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.

Like the brain, it is an excellent generator of maps for other sensory modalities such as encoding visual, auditory and somatosensory signals; it is not unreasonable to think of the hippocampus as a structure which generates maps of our environment and which guarantees our orientation in them..

Research has gone further and tested this paradigm in a wide variety of situations. We have seen, for example, that cells in place in labyrinth tasks are triggered when the animal makes mistakes or when it is in a position where the neuron would shoot normally (O’Keefe and Speakman, 1987). In tasks where the animal has to move through different spaces, locus neurons have been shown to fire depending on the origin and direction of the animal (Frank et al., 2000).

How space maps are formed

Another major focus of research in this area has been the way in which these spatial maps are formed. On the one hand, we might 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 in our brain circuits, that is, ‘that is to say 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 cells at the site, saw that when an animal is placed in a new environment, several minutes elapse. until these cells start to shoot normally. Therefore, site plans would be expressed, in some way, from the moment an animal enters a new environmentBut experience would change these cards in the future.

Therefore, one might think that brain plasticity plays a role in the formation of spatial maps. Then, if plasticity really played a role, one would expect mice to knock out the NMDA receptor for the neurotransmitter glutamate, i.e. mice that do not express this receptor – do not generate space maps. because this receptor plays a key role in brain plasticity and learning.

Plasticity plays an important role in the maintenance of spatial maps

However, this is not the case, and mice stricken with the NMDA receptor or mice that have been pharmacologically treated to block this receptor have been shown to express similar patterns of site cell response in new environments or parents. . 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.

Nonetheless, using logic, the mechanisms of brain plasticity must be clearly necessary for the memory stability of the newly formed maps. And, if not, what good would the experience of being trained by walking the streets of your city be? Wouldn’t we always have the feeling that this 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 appear, and in a way, despite an innate functioning of these functions, plasticity must play a role to keep these spatial maps in memory.

Network, management and on-board cells

It is quite abstract to speak of cells of place, and perhaps more than one reader has been surprised that the same area of ​​the brain that generates memories serves us, so to speak, as GPS. But we are not finished and the best is yet to come. Now let’s really turn more finely. At first, it was thought that spatial navigation would depend exclusively on the hippocampus when we saw that adjacent structures such as the entorhinal cortex showed very low activation as a function of space (Frank et al., 2000).

However, in these studies activity was recorded in the ventral areas of the entorhinal cortex and in later studies, Dorsal areas have been recorded that have higher connections with the hippocampus (Fyhn et al., 2004). therefore it has been observed that many cells in this region shoot according to position, similar to the hippocampus.. So far, these are expected results but when they decided to increase the area they would register in the entorhinal cortex, they had a surprise: among the groups of neurons that were activated according to space occupied by the animal existed. seemingly silent areas, i.e. they have not been activated. When the regions which showed 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 the cells of the network, we saw a possibility of solving the question of how the cells of the site are formed. Having the cells in place with many connections of the cells in the network, it is not unreasonable to think that they are formed from them. However, again, things are not that simple and experimental evidence has not confirmed this hypothesis. The geometric patterns that make up the cells of the network have not yet been interpreted either.

Navigation systems aren’t just about the hippocampus

The complexity does not end there. Even less when we have seen that navigation systems are not reduced to the hippocampus. This widened the limits of the research to other areas of the brain, uncovering other types of cells linked to cells at the site: steering cells and on-board cells.

The direction cells would encode the direction in which the subject moves and are located in the dorsal tegmental nucleus of the brainstem. On the other hand, border cells are cells that would increase their rate of fire as the subject approaches the limits of a given space and can be found in the subiculum – a specific region of the hippocampus -. Let’s offer a simplified example in which we will try to summarize the function of each cell type:

Imagine that you are in the dining room of your house and want to go to the kitchen. Since you are in the dining room of your house, you will have a place cell that will trigger while you stay in the dining room, but since you want to go to the kitchen, you will also have another place cell. activated which represents the kitchen. The activation will be clear because your home is a space that you know perfectly well and the activation will be able to detect it both in the place cells and in the cell network.

Now start walking towards the kitchen. There will be a group of specific direction cells that will now shoot and will not change until you maintain a specific direction. Now imagine that in order to get to the kitchen you have to turn right and go through a narrow hallway. The moment you turn, your steering cells will know it, and another set of steering cells will record the direction you have now taken by turning it on, and the previous ones will be turned off.

Also imagine that the hallway is narrow and any wrong movement can cause you to crash into the wall, so your on-board cells will increase their rate of fire. The closer you get to the hallway wall, the more the fire report will show its edge cells. Think of on-board cells as sensors that some new cars have that beep when you maneuver to park. On-board cells they work the same as these sensors, the closer it is to crashing – the louder they make. When you get to the kitchen your place cells will have indicated to you that it has arrived satisfactorily and being a larger environment your onboard cells will relax.

We just complicated everything

It is curious to think that our brain has some means of knowing our position. But there remains a question: how to reconcile declarative memory and spatial navigation in the hippocampus ?, i.e. how do our memories influence these maps? Or have our memories formed from these maps? To try to answer this question, we need to think a little further. Other studies have shown that the same cells that encode space, which we have already discussed, also encode time.. Thus, we have spoken of temporal cells (Eichenbaum, 2014) which encode the perception of time.

The surprising thing is that there is growing evidence to support the idea that place cells are the same as time cells. Then the same neuron using the same electrical impulses is able to encode space and time. The relationship between the encoding of time and space in these action potentials and their importance in memory remains a mystery.

In conclusion: my personal opinion

My opinion on the matter? Lifting my scientist’s robe 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, the brain gives us a simplified version of reality that it processes itself. In a similar way to the shadows in Plato’s cave. So just as quantum physics breaks down barriers to what we understand as reality, in neuroscience we have found that in the brain things are different from the world we consciously perceive and we need to have a very open mind to things that don’t. should not be. the way we really perceive them.

The only thing I’m clear about is something Antonio Damasio repeats often in his books: the brain is an excellent generator of maps. Maybe the brain interprets time and space the same way to form maps of our memories. And if you find that chimerical, think that Einsten, in his theory of relativity, one of the theories he postulated was that he couldn’t understand time without space, and vice versa. Unraveling these mysteries is certainly a challenge, especially since these are aspects that are difficult to study in animals.

However, no effort should be spared on these issues. First out of curiosity. If we are studying the expansion of the universe or the recently recorded gravitational waves, why don’t we go and study how our brains interpret time and space? And, on the other hand, many neurodegenerative pathologies such as Alzheimer’s disease have spatio-temporal disorientation as their first symptoms. Knowing the neurophysiological mechanisms of this coding, we could discover new aspects which will make it possible to better understand the pathological evolution of these diseases and, who knows, to discover new pharmacological or non-pharmacological targets.

Bibliographical references:

  • Eichenbaum H. 2014. Temporal cells in the hippocampus: a new dimension for memory mapping. Nature 15: 732-742
  • Frank LM, Brown EN, Wilson M. 2000. Trajectory encoding the hippocampus and the entorinal cortex. Neuron 27: 169-178.
  • Fyhn M, Molden S, Witter MP, Moser EI, Moser MB. 2004. Spatial representation in the entorinal cortex. Science 305: 1258-1264
  • Kentros C, Hargreaves E, Hawkins RD, Kandel ER, Shapiro M, Woman RV. 1998. Abolition of the long-term stability of new cellular maps of the hippocampal site by blocking the NMDA receptors. Science 280: 2121-2126.
  • Monaco JD, Abbott LF. 2011. Modular realignment of entorinal grid cell activity as a basis for hippocampal mapping. J Neurosci 31: 9414-9425.
  • O’Keefe J, Speakman A. 1987. Mono-unit activity in the rat hippocampus during a spatial memory task. Exp Brain Res 68: 1 –27.
  • Scoville WB, Milner B (1957). Recent memory loss after bilateral hippocampus. J Neurol Neurosurg Psychiatry 20: 11-21.

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