NMDA receptors of the nervous system: what they are and what functions they have

We know that our neurons communicate with each other through synapses, where neurotransmitters are involved. The main excitatory neurotransmitter in the brain is glutamate, which has different types of receptors. Here we are going to talk about one of them: NMDA receptors.

In this article, we’ll learn what these types of receptors are, what are their characteristics, how they work, and how they relate to memory, learning, and brain plasticity. Before that, however, we’ll do a brief introduction to the types of neurotransmitters that exist, to understand where glutamate is found.

    What are neurotransmitters and how are they classified?

    Neurotransmitters are biomolecules that allow the transmission of information between neurons (I.e. neurotransmission), by a chemical or electrical process (as the case may be) called a neuronal synapse.

    There are many types of neurotransmitters; the most accepted classification is that which divides them into three large groups:

    1. Amines

    Amines, in turn, are divided into quaternary amines (acetylcholine) and monoamines (which in turn are divided into: catecholamines and indolamines).

    2. Amino acids

    They include glutamate, GABA, glycine, and histamine.

    3. Neuropeptides

    For their part, neuropeptides include endorphins, encephalins, dinorphins and vasopressin.

    Glutamate and its NMDA receptors

    As we have seen, glutamate, also called glutamic acid, is an amino acid-like neurotransmitter in the brain. Glutamate is the quintessential brain excitatory neurotransmitter, And relates to multiple functions, in particular learning. It is located throughout the brain and also in the spinal cord.

    Like all neurotransmitters, glutamate has different types of receptors, which are structures located in cells (for example in neurons) through which neurotransmitters bind, enabling the synapse (which can be electrical or chemical).

    To understand it in a simple way and, in general, synapses are those connections between neurons that keep these nerve cells in constant communication and which allow the transmission of information, which makes it possible to carry out different processes: thinking, making decisions, being attentive, reasoning, speaking …

    Thus, glutamate has four types of receptors: NMDA receptors (which we will discuss in this article), AMPA receptors, kainate, and a type of metabotropic receptor.

    NMDA receivers: general characteristics

    NMDA receptors are very complex proteins that act as glutamate receptors Functionally, NMDA receptors, as well as AMPA glutamate receptors, are mainly linked to two cognitive processes: learning and memory. More specifically, NMDA receptors are essential, above all, for memory. Outraged, they are also strongly linked to neuronal or synaptic plasticity.

    On the other hand, NMDA receptors have also been linked to the origin of various pathologies or diseases, such as: epilepsy, certain neurodegenerative diseases (such as Alzheimer’s, Parkinson’s and Huntington’s disease), schizophrenia or stroke.


      What do the acronyms NMDA mean? They are the acronym for “N-methyl D-aspartate”, Which is a selective agonist responsible for the specific binding of these types of glutamate receptors, but not others. When such receptors are activated, non-selective ion channels are opened for all kinds of cations (positively charged ions).

      The receptors are activated by a power differential when the magnesium ions (Mg2 +) come into contact. this step allows sodium ions (Na +), calcium ions (Ca2 +) (these in smaller amounts) and potassium ions (K +) to circulate.

      The flow of calcium ions, in particular, is essential for improving the processes of synaptic plasticity or brain plasticity. This type of plasticity consists in the fact that external stimuli cause the potentiation of certain synapses and the weakening of others.

      Thus, synaptic, cerebral or neuronal plasticity allows neurons to function correctly, to communicate with each other and to modulate their activity according to the environment and environmental stimuli. In short, it allows the brain to adapt to changes and also helps to maximize its functions.

      A type of ionotropic receptor

      At the structural and functional level, NMDA receptors, also called NMDAR, are ionotropic receptors. But let’s take a step back; there are three types of brain receptors: ionotropic (such as NMDA receptors), metabotropic, and autoreceptors. Compared to the other two, ionotropic receptors are faster.

      Their main feature is that they function as specific ion channels for certain ions, i.e. the receptor itself acts as a channel.

      the functions

      NMDA receptors, along with glutamate, are associated with a multitude of nervous system (SN) functions. They are mainly responsible for regulating the excitatory post-synaptic potential of cells.. In addition, as we have seen, NMDA receptors play an essential role in processes such as: neural plasticity, memory and learning.

      On the other hand, some studies also mention the role played by the binding of glutamate to NMDA receptors in cell migration processes.

      1. Neural (or synaptic) plasticity

      Neuronal plasticity and its relationship to NMDA receptors have been extensively studied. It is known that the activation and consolidation of certain synapses, especially during development (Although also in adults), they make possible the maturation of the circuits of the SN, that is to say, they foment its functional connections.

      All of this happens through neural plasticity, which is heavily dependent on NMDA receptors.

      More precisely, NMDA receptors are activated in the face of a very specific type of synaptic plasticity, called long-term potentiation (LTP). Most memory and learning processes are based on this form of plasticity

      2. Memory

      In terms of the link with memory, it has been shown how NMDA receptors play an essential role in processes involving memory formation; this includes a type of memory called episodic memory (The one that allows us to remember our lived experiences and that shapes our autobiography).

        3. Learning

        Finally, NMDA receptors are also linked to learning processes, and their activation has been observed in the face of such processes, which in turn are linked to memory and brain plasticity.

        Bibliographical references:

        • Flors-Soto, ME, Chaparro-Horta, V., Escoto-Delgadillo, M., Vazquez-Valls, I., González-Castañeda, RE and Beas-Zarate, C. (2012). Structure and function of NMDA-type glutamate receptor subunits. Neurology (English edition), 27 (5): 301-310.
        • Morgado, I. (2005). Psychobiology of learning and memory: foundations and recent progress. Rev Neurol, 40 (5): 289-297.
        • Rosenweig, MR, Breedlove, SM and Watson, NV (2005). Psychobiology: an introduction to behavioral, cognitive and clinical neuroscience. Barcelona: Ariel.
        • Stahl, SM (2002). Essential psychopharmacology. Neuroscientific bases and clinical applications. Barcelona: Ariel.
        • Vyklick, V; Korinek, M; Smejkalov, T; Balik, A; Krausova, B; Kaniakova, M. (2014). Structure, function and pharmacology of NMDA receptor channels. Czech Republic: Institute of Physiology vvi, Academy of Sciences of the Czech Republic, 63 (Suppl. 1): S191-S203.

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