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

It makes good sense that the more you study, the more information is stored in the brain. It is for this reason that, rather than abruptly studying the day before an exam, it is recommended that you devote half an hour a day to it for the previous two weeks.

All of this is already obvious, but, while it makes good sense, what we don’t know so well is what its physiological explanation is. What changes are happening in the brain so that we can retain information?

So good, the biochemical process in the brain that is responsible for learning and memory is called long-term potentiation, And this is a very interesting aspect of our brain that we will learn about below.

    What is long term empowerment?

    Long-term empowerment is a process that occurs in the membrane of the neuron that explains how it is possible to regulate learning and what are their physiological bases. The process occurs when information is examined multiple times, making the neuron sensitized and more responsive to lower action potentials, making it easier to remember what has been learned.

    The concept is quite complex, and before explaining it in any more depth, it is necessary to revisit its historical context and then to examine in more detail how the process itself unfolds.

    Historical context

    Years ago, scientists were looking for the exact location in the brain where brain functions took place. They later found out that several parties can participate in the same function. We know that in learning and memory, several structures are involved: the hippocampus, the amygdala, the brain and the basal ganglia.

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

    Prior to studying Aplysia, a scientist named Donald Hebb in 1949 proposed a hypothesis to understand the change at the cellular level that occurs during learning. He suggested that during learning, a metabolic change occurs in neurons. However, it wasn’t until 1973 that Terje Lømo, a Norwegian physiologist studying the rat hippocampus, discovered an unexpected phenomenon: long-term potentiation, with Hebb suspecting this neuronal metabolic change.

    How is long-term empowerment given?

    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. This can be checked, in a practical way, when we are studying for an exam. While we study, we activate several pathways within our brain, pathways by which we have managed to store, by repetition, the information that we have examined. The more information is revised, the more it will be retained.

    Long-term memory has been fundamentally associated with a structure, the shape resembling that of a hippocampus: the hippocampus. This brain structure is located in the medial temporal lobe of both hemispheres, and is what is responsible for the coordination of information storage and memory retrieval. The research focused on this part of the brain, when they tried to study the learning process, in particular various structures of the same: tooth rotation, CA1 and CA3.

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

    This whole process is long-term empowerment, which it is the cellular and molecular process of memory. This long-term potentiation implies a lasting improvement in signal transmission between two neurons after repeated stimulation. This process has been mainly studied at the level of synapses between Schaffer collaterals and CA1 field neurons.

    Observation of synapses between CA3 and CA1 cells reveals multiple structures linked to long-term potentiation. NMDA and AMPA receptors can be found in the postsynaptic neuron which are usually found together. 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, that is, it allows them to penetrate inside 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 moves along the presynaptic axon of Schaffer’s collaterals occurs the release of glutamate, a neurotransmitter that fuses with AMPA and NMDA receptors. When this electrochemical stimulus is weak, the amount of glutamate released is low.

    AMPA receptors are opened and a small amount of sodium enters the neuron, causing a small depolarization, that is, the electrical charge of the neuron increases. Glutamate also binds to NMDA receptors, but no ions will be able to pass because the magnesium ion continues to block.

    When the received signal is small, the postsynaptic response is not sufficient to elicit the output of the magnesium ion, so long-term potentiation is not given. This is a situation that can occur, for example, when you have been studying for a very short time. A high frequency of action potentials was not activated because it has been so little studied, so it did not induce this knowledge retention process.

    In contrast, when a high frequency of action potentials occurs, traveling through Schaffer’s collateral axons, more glutamate is released into the synaptic space. This can be achieved if more is studied, as a higher frequency of action potentials is encouraged. Glutamate will bind to AMPA receptors, causing more sodium to enter the neuron because the channel stays open longer.

    The more sodium the cell contains, it becomes depolarized, Successfully repel magnesium ion from the NMDA receptor through a process called electrostatic repulsion. At this point, the glutamate-activated NMDA receptor allows sodium and calcium to enter through its pores. NMDA receptors are called voltage-gated and ligand-gated receptors because they require pre- and postsynaptic excitation for the opening of the channel: fusion of the released presynaptic glutamate and depolarization of the postsynaptic cell.

      Strengthening of synapses

      Long-term empowerment is a process that this implies that the connection between two neurons is 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 stage

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

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

      Late phase

      During the late phase, a higher calcium intake is given, This causes the activation of genetic transcription factors that cause the synthesis of new proteins. Some of these proteins will eventually be new AMPA receptors, which will be inserted into the neuronal membrane.

      In addition, there is an increase in protein synthesis of growth factors, which lead to the growth of new synapses and are the basis of synaptic plasticity. So in this way the brain changes as it is taken.

      These synapses are formed between the CA1 and CA3 neurons, Allowing a stronger connection. Late phase changes are longer 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 which will allow even with low frequencies of potentials to ‘action, cellular depolarization is created when previously a high frequency of potentials had to be given 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 areas of the brain, including the cerebral cortex. Either way, it should be clear that the more you study, the more pathways are activated throughout the brain, making learning a bit more consolidated.

      Bibliographical references:

      • Abraham WC, Bear MF (1996): Metaplasticity, plasticity of synaptic plasticity. Trends in neuroscience, 19126-130
      • Agranoff BW, Uhler M (1994): Learning and memory. In: Basic Neurochemistry, Molecular, Cellular, and Medical Aspects, 5th ed., Ed. By GJ Siegel. Raven Press, N. York, 1025-1045.
      • Paradiso, Michael A .; Bear, Mark F .; Connors, Barry W. (2007). Neurosciences: exploration of the brain. Hagerstwon, MD: Lippincott Williams and Wilkins.

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