Long-term potentiation: what is it and how does it explain learning?

Long-term potentiation shows the neural basis of learning.

It is common sense that the more you study, the more information is retained in your brain. It is for this reason that, rather than studying all at once the day before an exam, it is recommended to dedicate half an hour a day during the two weeks prior to the exam.

All this is already obvious, however, although it is common sense, what we do not know so well is what is its physiological explanation. What changes occur in the brain so that we manage to retain information?

Well, the biochemical process at the brain level that is behind learning and memory is called long-term potentiation, and it is a very interesting aspect of the brain.and it is a very interesting aspect of our brain that we are going to learn next.

What is long-term potentiation?

Long-term potentiation is a process occurring in the membrane of the neuron that explains how learning can take place and its physiological basis.. The process occurs when a piece of information is repeated several times, causing the neuron to become more sensitive and reactive to lower action potentials, making it easier to remember what has been learned.

The concept is quite complex, and before explaining it in more depth, it is necessary to review its historical background and then look in more detail at how the process itself occurs.

Historical background

Years ago, scientists were searching for the exact place in the brain where brain functions occurred. Later, they discovered that different parts of the brain can be involved in the same function. It is known that several structures are involved in learning and memory: hippocampus, amygdala, cerebral and basal ganglia.

In 1970 an American scientist named Eric Kandel studied the sea slug Aplysia, in which he was able to discover some biochemical phenomena that occur in neurons while learning. It may seem surprising to relate a slug to the human brain, although it is clear that their brains are not the same, the slug being an invertebrate. However, despite the differences between vertebrate and invertebrate nervous systems, the brain chemistry of the neuron, action potentials and neurotransmitters are the same..

Prior to the studies in Aplysia, a scientist named Donald Hebb proposed, in 1949, a hypothesis to understand the cellular-level change that occurs during learning. He suggested that when learning occurs, a metabolic change occurs in the neurons. However, it was not until 1973 when Terje Lømo, a Norwegian physiologist, studying the hippocampus of rats, discovered an unexpected phenomenon: long-term potentiation, a neuronal metabolic change suspected by Hebb.

How does long-term potentiation occur?

The human brain has the capacity to store information, either for short periods of time, in short-term memory, or for life, in long-term memory.in long-term memory. This can be seen, in a practical way, when we study for an exam. While we are studying, we activate several pathways inside our brain, pathways with which we manage to store, through repetition, the information we have reviewed. The more the information is reviewed, the more it will be retained.

Long-term memory has been associated primarily with a structure whose shape resembles that of a seahorse: the hippocampus. This brain structure is located in the medial temporal lobe of both hemispheres, and is responsible for the coordination of information storage and retrieval of information. is responsible for coordinating the storage of information and the retrieval of memories.. Research has focused on this part of the brain when trying to study the learning process, especially several structures of the brain: the dentate gyrus, the CA1 and CA3.

The process of memorization begins when information reaches the dentate gyrus from the entorhinal cortex.. The axons of the granular neurons project their axons to the cells of area CA3, which in turn project the information through the so-called Schaffer collaterals to the cells of field CA1, and from there, through the subiculum, the information returns to the entorhinal cortex.

This whole process is long-term potentiation, which is the cellular and molecular process of is the cellular and molecular process of memory.. This long-term potentiation involves the lasting enhancement of signal transmission between two neurons after repeated stimulation. This process has been mostly studied at synapses between Schaffer collaterals and CA1 field neurons.

Looking at the synapses between CA3 and CA1 cells reveals multiple structures that are related to long-term potentiation. In the postsynaptic neuron, NMDA and AMPA receptors can be found, which are normally found together. receptors can be found in the postsynaptic neuron. These receptors are activated after the neurotransmitter fuses with the cell membrane and is released into the space between neurons.

The AMPA receptor is permeable to sodium ions, i.e. it allows them to enter the interior of the neuron. The NMDA receptor is also permeable to sodium ions, but it is also permeable to calcium ions. NMDA receptors are blocked by a magnesium ion, which prevents sodium and calcium ions from entering the cell.

When an action potential travels along the presynaptic axon of Schaffer's collaterals it causes release of glutamate, a neurotransmitter that fuses with AMPA and NMDA receptors.. When this electrochemical stimulus is of low power, the amount of glutamate released is low.

The AMPA receptors open and a small amount of sodium enters the neuron, causing a small depolarization to occur, i.e., increasing the electrical charge of the neuron. Glutamate also binds to the NMDA receptors, but no ion will be able to pass through because the magnesium ion continues to block it.

When the received signal is small, the postsynaptic response is not sufficient to achieve the output of the magnesium ion, so long-term potentiation does not occur. This is a situation that can occur, for example, when one has been studying for a very short time. A high frequency of action potentials have not been activated because they have been studied for such a short time, so this process of knowledge retention has not been induced.

On the other hand, when a high frequency of action potentials is present, traveling along the Schaffer collateral axons, an increased amount of glutamate is released into the synaptic space.. This can be achieved if further study is done, since a higher frequency of action potentials is promoted. Glutamate will bind to AMPA receptors, causing more sodium to enter the neuron because the channel remains open longer.

More sodium entering the interior of the cell leads to depolarization of the cell, causing it to repel the sodium ion.The NMDA receptor's magnesium ion is repelled by a process called electrostatic repulsion. At this point, the glutamate-activated NMDA receptor allows sodium and calcium to enter through its pore. NMDA receptors are called voltage- and ligand-dependent receptors because they require both presynaptic and postsynaptic excitation for channel opening: fusion of the released presynaptic glutamate and depolarization of the postsynaptic cell.

Strengthening of synapses

Long-term potentiation is a process that involves the involves the connection between two neurons being strengthened.. The introduction of calcium into the postsynaptic neuron acts as a second messenger, activating multiple intracellular processes. The increase in calcium leads to two processes involved in long-term potentiation: the early phase and the late phase.

Early phase

During the early phase, calcium fuses with its fusion proteins.causing the insertion of new AMPA channels in the cell membrane of the synapse between the cells of the CA1 and CA3 field.

These new AMPA receptors were stored inside the neuron, and are only released thanks to the influx of calcium coming from the NMDA receptor. Thanks to this, AMPA channels will be available in future synaptic connections. The changes induced during the early phase only last a few hours.

Late phase

During the late phase there is an increased influx of calciumThis triggers the activation of gene transcription factors that cause new proteins to be synthesized. Some of these proteins will eventually become new AMPA receptors, which will be inserted into the neuronal membrane.

In addition, there is an increase in the synthesis of growth factor proteins, which lead to the growth of new synapses and are the basis of synaptic plasticity. Thus, in this way, the brain changes as it is learning.

These synapses form between CA1 and CA3 neurons, allowing a stronger connection.allowing for a stronger connection. Late phase changes are more long-lasting, ranging from 24 hours to a lifetime.

It should be noted that long-term potentiation is not a mechanism, but an increase in activity between two neurons, which results in an increase in the AMPA channels of the neurons that will allow, even at low frequencies of action potentials, cell depolarization to be created when, previously, a high frequency of potentials was necessary to achieve such a goal.

This whole process is the foundation of memory. However, it should be noted that the hippocampus is not the only region where long-term potentiation occurs.. Memory processing occurs in many other brain regions, including the cerebral cortex. Be that as it may, it should be clear that the more one studies, the more pathways are activated throughout the brain, making learning become more consolidated.

Bibliographical references:

• Abraham WC, Bear MF (1996): Metaplasticity, the plasticity of synaptic plasticity. Trends in Neuroscience,19,126-130.
• Agranoff BW, Uhler M (1994): Learning and memory. In: Basic Neurochemistry, Molecular, Cellular, and Medical aspects, 5th Ed. Raven Press, N. York, 1025-1045.
• Paradiso, Michael A.; Bear, Mark F.; Connors, Barry W. (2007). Neuroscience: Exploring the Brain. Hagerstwon, MD: Lippincott Williams & Wilkins.