Synapses may not be the basis of memory

The neuroscientific clues linking our learning to memory.

The brain contains thousands upon thousands of interconnections between its neurons, which are separated by a small space known as a synapse. It is here that the transmission of information passes from neuron to neuron..

It has been seen for some time now that the activity of the synapse is not static, i.e. it is not always the same. It can be enhanced or diminished as a consequence of external stimuli, such as things we experience. This quality of being able to modulate synapses is known as brain plasticity or neuroplasticity.

Until now, it has been assumed that this ability to modulate synapses actively participates in two activities that are so important for brain development: learning and memory. I say until now, since there is a new alternative current to this explanatory scheme, according to which synapses are not as important in understanding the functioning of memory as is commonly believed. synapses are not as important as is commonly believed.

The history of synapses

Thanks to Ramón y Cajal, we know that neurons do not form a unified tissue, but that they are all separated by interneuronal spaces, microscopic places that Sherrington would later call "synapses". Decades later, the psychologist Donald Hebb offered a theory according to which synapses are not always the same over time and can be modulated, that is, he spoke of what we know as neuroplasticity: two or more neurons can cause the relationship between them to consolidate or to degrademaking certain communication pathways more frequent than others. As a curious fact, fifty years before postulating this theory, Ramón y Cajal left evidence of the existence of this modulation in his writings.

Today we know of two mechanisms used in the process of brain plasticity: long-term potentiation (LTP), which is an intensification of the synapse between two neurons; and long-term depression (LTD), which is the opposite of the former, i.e., a reduction in the transmission of information.

Memory and neuroscience, empirical evidence with controversy

Learning is the process by which we associate things and events in life to acquire new knowledge. Memory is the activity of maintaining and retaining this learned knowledge over time. Hundreds of experiments have been conducted throughout history in search of how the brain performs these two activities.

A classic in this research is the work of Kandel and Siegelbaum (2013) with a small invertebrate, the marine snail known as Aplysia. In this research, they saw that changes in synaptic conductance were generated as a consequence of how the animal responds to the environment, demonstrating that synaptic synapses are generated as a consequence of how the animal responds to the environment.demonstrating that synapses are involved in the process of learning and memorizing. But a more recent experiment with Aplysia by Chen et al. (2014) has found something that clashes with the conclusions previously reached. The study reveals that long-term memory persists in the animal in motor functions after the synapse has been inhibited by drugs, casting doubt on the idea that the synapse is involved in the entire memory process.

Another case supporting this idea arises from the experiment proposed by Johansson et al. (2014). On this occasion, Purkinje cells in the cerebellum were studied. These cells have among their functions that of controlling the rhythm of movements, and when stimulated directly and under drug inhibition of synapses, against all odds, they continued to set the rhythm. Johansson concluded that their memory is not influenced by external mechanisms, and that it is the Purkinje cells themselves that control the mechanism individually, independent of the influences of synapses.

Finally, a project by Ryan et al. (2015) served to demonstrate that synapse strength is not a critical point in memory consolidation. According to their work, injecting protein inhibitors into animals results in retrograde amnesia, i.e., they cannot retain new knowledge. But if, in the same situation, we apply small flashes of light that stimulate the production of certain proteins (a method known as optogenetics), memory can be retained despite the induced chemical blockade.

Learning and memory, linked or independent mechanisms?

In order to memorize something, we first have to learn about it.. I don't know if it is because of this, but the current neuroscientific literature tends to lump these two terms together and the experiments on which they are based often have an ambiguous conclusion, which does not allow us to distinguish between learning and memory processes, making it difficult to understand whether they use a common mechanism or not.

A good example is the work of Martin and Morris (2002) in the study of the hippocampus as a learning center. The basis of the research focused on N-Methyl-D-Aspartate (NMDA) receptors, a protein that recognizes the neurotransmitter glutamate and is involved in LTP signaling. They showed that without long-term potentiation in cells of the hypothalamus, it is impossible to learn new knowledge. The experiment consisted of administering NMDA receptor blockers to rats, which were left in a water canister with a raft, and were unable to learn the location of the raft by repeating the test, unlike rats without inhibitors.

Subsequent studies reveal that if the rat receives training prior to the administration of inhibitors, the rat "compensates" for the loss of LTP, i.e., it has memory. The conclusion to be shown is that LTP is actively involved in learning, but it is not so clear that it is involved in information retrieval..

The implication of brain plasticity

There are many experiments showing that neuroplasticity is actively involved in the acquisition of new knowledge.The role of glutamate in memory, for example in the case mentioned above, or in the creation of transgenic mice in which the gene for glutamate production is eliminated, which severely hampers the animal's learning.

Instead, its role in memory is beginning to be more in doubt, as you have been able to read with a few examples cited. A theory has begun to emerge that the mechanism of memory lies within cells rather than at synapses. But as psychologist and neuroscientist Ralph Adolph points out, neuroscience will figure out how learning and memory work within the next fifty years.that is, only time will tell.

Bibliographical references:

• Chen, S., Cai, D., Pearce, K., Sun, P. Y.-W., Roberts, A. C., & Glanzman, D. L. (2014). Reinstatement of long-term memory following erasure of its behavioral and synaptic expression in Aplysia. eLife 3:e03896. doi: 10.7554/eLife.03896.
• Johansson, F., Jirenhed, D.-A., Rasmussen, A., Zucca, R., y Hesslow, G. (2014). Memory trace and timing mechanism localized to cerebellar Purkinje cells. Proc. Natl. Acad. Sci. U.S.A. 111, 14930–14934. doi: 10.1073/pnas.1415371111.
• Kandel, E. R., y Siegelbaum, S. A. (2013). “Cellular mechanisms of implicit memory storage and the Biological basis of individuality,” en Principles of Neural Science, 5th Edn., eds E. R. Kandel, J. H. Schwartz, T. M. Jessell, S. A. Siegelbaum, y A. J. Hudspeth (New York, NY: McGraw-Hill), 1461–1486.
• Martin, S. J., y Morris, R. G. M. (2002). New life in an old idea: the synaptic plasticity and memory hypothesis revisited. Hippocampus 12, 609–636. doi: 10.1002/hipo.10107.
• Ryan, T. J., Roy, D. S., Pignatelli, M., Arons, A., y Tonegawa, S. (2015). Engram cells retain memory under retrograde amnesia. Science 348, 1007–1013. doi: 10.1126/science.aaa5542.