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

What are NMDA receptors and what are their functions in the neurons of the nervous system?

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 will talk about one of them: NMDA receptors.

In this article we will learn what these receptors are, what characteristics they have, how they work and how they are linked to memory, learning and brain plasticity. However, first we will make a brief introduction on the types of neurotransmitters that exist, to understand where glutamate is located.

What are neurotransmitters and how are they classified?

Neurotransmitters are biomolecules that enable the transmission of information between neurons (i.e. neurotransmission), through a chemical or electrical process (depending on the case) called neuronal synapse. (i.e. neurotransmission), through a chemical or electrical process (depending on the case) called neuronal synapse.

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

The neuropeptides include endorphins, enkephalins, dynorphins and vasopressin..

Glutamate and its NMDA receptors

As we have seen, glutamate, also called glutamic acid, is an amino acid-type brain neurotransmitter. Glutamate is the excitatory neurotransmitter of the brain par excellence.and is related to multiple functions, especially learning. It is localized throughout the brain, and also in the spinal cord.

Like all neurotransmitters, glutamate has different types of receptors, which are structures located in cells (e.g. in neurons) where neurotransmitters bind, allowing synapses (which can be electrical or chemical).

To understand it in a simple way and, in broad strokes, synapses are those connections between neurons that keep these nerve cells in constant communication and allow the transmission of information, which can be electrical or chemical. and that allow the transmission of information, which makes possible the achievement of different processes: thinking, making decisions, paying attention, reasoning, speaking...

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

NMDA receptors: general characteristics

NMDA receptors are very complex proteins that act as glutamate receptors. At the functional level, NMDA receptors, together with glutamate AMPA receptors, are fundamentally related to two cognitive processes: learning and memory. Specifically, NMDA receptors are essential, above all, for memory. In addition, they are also strongly linked to plasticity, they are also strongly linked to neuronal or synaptic plasticity..

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

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Function

What does the acronym NMDA stand for? It is the acronym for "N-methyl D-aspartate", which is a selective agonist.which is a selective agonist responsible for binding specifically this type of glutamate receptors, but not others. When these receptors are activated, non-selective ion channels open for all kinds of cations (positively charged ions).

The receptors are activated by a power differential, when magnesium ions (Mg2+) come into contact with them. This step enables the flow of sodium ions (Na+), calcium ions (Ca2+) (these in smaller quantities) and potassium ions (K+)..

The flow of calcium ions, specifically, is fundamental to enhance 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, communicate with each other and modulate their activity according to the environment and environmental stimuli. In short, it allows the brain to adapt to changes and also enables its functions to be maximized.

A type of ionotropic receptor

Structurally and functionally, NMDA receptors, also called NMDAr, are ionotropic receptors.. But let's back up a bit; there are three types of brain receptors: ionotropic receptors (such as NMDA receptors), metabotropic receptors and autoreceptors. Compared to the other two, ionotropic receptors are faster.

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

Functions

NMDA receptors, together with glutamate, are involved in a multitude of functions of the nervous system (SN). They are mainly responsible for regulating the excitatory postsynaptic potential of the cells.. Furthermore, as we have seen, NMDA receptors play an essential role in processes such as neuronal plasticity, memory and learning.

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

1. Neuronal (or synaptic) plasticity

Neuronal plasticity and its relationship with NMDA receptors has been extensively studied. It is known that the activation and consolidation of certain synapses, especially during development (although also in adults), make possible the maturation of the (although also in adults), enable the maturation of SN circuits, i.e., promote their functional connections.

All this occurs thanks to neuronal plasticity, which depends to a large extent on NMDA receptors.

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

Memory

As for their link to memory, it has been shown that NMDA receptors play an essential role in the processes involved in memory formation. includes a type of memory called episodic memory (the one that allows us to remember (the one that allows us to remember lived experiences and that shapes our autobiography).

3. Learning

Finally, NMDA receptors are also linked to learning processes, and it has been seen how their activation is produced before this type of processes, which is related, in turn, to memory and brain plasticity.

Bibliographical references:

• Flores-Soto, M.E., Chaparro-Huerta, V., Escoto-Delgadillo, M., Vazquez-Valls, E., González-Castañeda, R.E. & 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: fundamentals and recent advances. Rev Neurol, 40 (5): 289-297.
• Rosenweig, M.R., Breedlove, S.M & Watson, N.V. (2005). Psychobiology: an introduction to behavioral, cognitive and clinical neuroscience. Barcelona: Ariel.
• Stahl, S.M. (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 v.v.i., Academy of Sciences of the Czech, 63(Suppl. 1): S191-S203.