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 home, our neighborhood, to go to work.

We also depend on it when we travel to a new and unfamiliar city. We use it even when we are driving and, possibly, the reader has sometimes been the victim of an oversight in his or her orientation or that of a colleague, which has condemned him or her to getting lost and having to drive around until he or she has found the right route.

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

These are all situations that tend to frustrate us quite a bit and lead us to curse our orientation or that of others with insults, shouts and various behaviours. Well, because today I will give a brushstroke on the neurophysiological mechanisms of orientation , on our brain GPS to understand us.

We will start by being specific: we should not curse orientation as this is only a product of our neuronal activity in specific regions. Therefore, we will start by cursing our hippocampus.

The hippocampus as brain structure

Evolutionarily, the hippocampus is an ancient structure, it is part of the archaicortex, 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 substratum of memory, emotions, learning and motivation.

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

Proof of this is the abundant studies that exist about the popular case of the “MH patient”, a patient who had both his 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 study this case further, I recommend the studies of Scoville and Millner (1957) who studied the MH patient extensively.

The Place Cells: what are they?

So far we’ve said nothing new, nothing surprising. But it was in 1971 when by chance a fact was discovered that led to 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 behavioural tests, the animal was awake, conscious and moving freely.

What they didn’t expect to discover was that there were neurons that responded selectively according to the area in which the rat was located. It is not that there were specific neurons for each position (there is no neuron for its bathroom, for example), but that cells were observed in the CA1 (a specific region of the hippocampus) that marked reference points that could adapt to different spaces.

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

Innate programming vs. experience

This discovery perplexed many neuroscientists who considered the hippocampus to be a declarative learning structure and now saw how it was capable of encoding spatial information. This gave rise to the “cognitive mapping” hypothesis that would postulate 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 guarantees our orientation in them .

Research has gone further and tested this paradigm in a variety of situations. It has been seen, for example, that the cells in place in maze tasks fire when the animal makes mistakes or when it is in a position where the neuron would normally fire (O’keefe and Speakman, 1987). In tasks where the animal must move through different spaces, it has been observed that the locus neurons fire depending on where the animal comes from and where it is going (Frank et al., 2000).

How space maps are formed

Another major focus of research 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, that is, innate. The question is still not 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 from place, have seen that when an animal is placed in a new environment, several minutes pass until these cells begin to shoot normally. Thus, the place maps would be expressed, in some way, from the moment an animal enters a new environment , but experience would make modify these maps in the future.

Therefore, we might think that brain plasticity is playing a role in the formation of spatial maps. Then, if plasticity really played a role we would expect knockout mice to the NMDA receptor of the neurotransmitter glutamate – that is, mice which do not express this receptor – not to 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 knockout mice to the NMDA receptor or mice that have been pharmacologically treated to block this receptor, have been found to express similar patterns of response of the cells in place in new or familiar environments. This suggests that spatial mapping expression 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, the mechanisms of brain plasticity must clearly be necessary for the memory stability of newly formed maps. And, if this were not the case, what use would be the experience that one forms by walking the streets of one’s city? Would we not always have the feeling that it is the first time that we enter our house? I believe that, as on so many other occasions, the hypotheses are more complementary than they seem and, in some way, despite the innate functioning of these functions, plasticity must play a role in the maintenance of these spatial maps in the memory .

Network, steering and edge cells

It is quite abstract to talk about place cells and possibly more than one reader has been surprised that the same brain area that generates memories serves us, so to speak, as GPS. But we’re not finished, and the best is yet to come. Now let’s really curl up. Initially, 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 spatial activation (Frank et al., 2000).

However, these studies recorded activity in ventral areas of the entorhinal cortex and subsequent studies recorded dorsal areas which have a greater number of connections to the hippocampus (Fyhn et al., 2004). Thus it was observed that many cells from this region fired as a function of position, similar to the hippocampus . So far, these are results that were expected to be found, 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 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 were observed in the form of hexagons or triangles. They called these neurons in the entorhinal cortex “network cells”.

The discovery of the network cells was seen as a possibility to solve the question of how the cells are formed from place. Since the cells of place have numerous connections to the network cells, it is not unreasonable to think that they are formed from them. However, once again, things are not so simple and experimental evidence has not confirmed this hypothesis. The geometrical patterns that form the network cells have not yet been interpreted either.

Navigation systems are not reduced to the hippocampus

The complexity doesn’t end here. Even less so when it has been seen that navigation systems are not reduced to the hippocampus. This has pushed the boundaries of research to other areas of the brain, thus discovering other types of cells related to the cells of place: the direction cells and the edge cells .

The direction cells would encode the direction in which the subject moves and would be located in the dorsal tegmental nucleus of the brain stem. On the other hand, border cells are cells that would increase their rate of firing as the subject approaches the boundaries of a given space and can be found in the subcurriculum -specific region of the hippocampus. We will offer a simplified example in which we will try to summarize the function of each cell type:

Imagine you’re 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 while you are in the dining room, but since 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 and 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 direction cells that will now be firing and will not change as long as you maintain a specific direction. Now, imagine that to get to the kitchen you have to turn right and cross a narrow corridor. The moment you turn, your direction cells will know and another set of direction cells will register the direction you have now taken by firing, and the previous ones will be deactivated.

Also imagine 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 wall in the corridor, the higher your edge cells will show. Think of the edge cells as the sensors that some new cars have that make an audible signal when you’re maneuvering to park. The edge cells work in a similar way to these sensors, the closer you are to bumping into each other the more noise they make . When you get to the kitchen, your parking cells will have indicated that it has arrived satisfactorily and as it is a larger environment, your edge cells will relax.

Let’s just make it all complicated

It’s funny to think that our brain has ways of knowing our position. But one 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 are 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, we have talked about the time cells (Eichenbaum, 2014) which would encode the perception of time.

The surprising thing about this case is that there is more and more evidence supporting the idea that the cells of place are the same as the cells of time . Then, the same neuron by means of the same electrical impulses is able to encode space and time. The relationship between the coding of time and space in the same action potentials and its importance in memory remains a mystery.

In conclusion: my personal opinion

My opinion on that? Taking off my scientist’s coat, I can say that the human being is used to think about 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 of Plato’s cave. Thus, just as in quantum physics barriers are broken down from what we understand as reality, in neuroscience we discover that in the brain things are different from the world we consciously perceive and we must have a very open mind that things do not have to be as we actually perceive them.

The only thing I am clear about is something that Antonio Damasio usually repeats 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 you think it is chimerical, 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. Undoubtedly, unraveling these mysteries is a challenge, even more so when they are difficult to study in animals.

However, no effort should be spared in these matters. Firstly, out of curiosity. If we study the expansion of the universe or gravitational waves, recently recorded, why wouldn’t we study how our brain interprets time and space? And, secondly, many of the neurodegenerative pathologies such as Alzheimer’s disease have as their first symptoms spatial-temporal disorientation. By 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. Células de tiempo en el hipocampo: una nueva dimensión para el mapeo de las memorias. Naturaleza 15: 732-742
  • Frank LM, Brown EN, Wilson M. 2000. Codificación de la trayectoria en el hipocampo y la corteza entorrinal. Neurona 27: 169-178.
  • Fyhn M, Molden S, Witter MP, Moser EI, Moser M-B. 2004. Representación espacial en la corteza entorrinal. Ciencia 305: 1258-1264
  • Kentros C, Hargreaves E, Hawkins RD, Kandel ER, Shapiro M, Muller RV. 1998. Abolición de la estabilidad a largo plazo de los nuevos mapas de células del lugar del hipocampo por bloqueo del receptor NMDA. Ciencia 280: 2121-2126.
  • Mónaco JD, Abbott LF. 2011. Reajuste modular de la actividad celular de la rejilla entorrinal como base para el remapeo del hipocampo. J Neurosci 31: 9414-9425.
  • O’Keefe J, Speakman A. 1987. Actividad de una sola unidad en el hipocampo de las ratas durante una tarea de memoria espacial. Exp Brain Res 68: 1 -27.
  • Scoville WB, Milner B (1957). Pérdida de la memoria reciente después de la hipocampesión bilateral. J Neurol Neurosurgia Psiquiatría 20: 11-21.