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

In this article we will know what these types of receptors are, what their characteristics are, how they work and how they are linked to memory, learning and brain plasticity. However, first we will make a brief introduction about 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.

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

1. Amines

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

2. Amino acids

They include glutamate, GABA, glycine and histamine.

3. Neuropeptides

Neuropeptides include endorphins, encephalines, 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 brain’s quintessential excitatory neurotransmitter , and is related to multiple functions, especially 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 on cells (for example in neurons) where neurotransmitters bind, allowing synapses (which can be electrical or chemical).

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

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

NMDA receivers: general characteristics

NMDA receptors are very complex proteins that act as receptors for glutamate. Specifically, NMDA receptors are essential, above all, for memory. Moreover, 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 diseases), schizophrenia or strokes.

Operation

What does NMDA stand for? This is the acronym for “N-methyl D-aspartate” , which is a selective agonist that specifically binds this type of glutamate receptor, but not others. When this type of receptor is activated, non-selective ion channels are opened for all kinds of cations (ions with a positive electrical charge).

The receivers are activated by a power differential, when the Magnesium ions (Mg2+) come into contact. This step allows sodium (Na+), calcium (Ca2+) ions (these in smaller quantities) and potassium (K+) ions to flow .

The flow of calcium ions, in a specific way, is essential to enhance the processes of synaptic plasticity or brain plasticity. This type of plasticity consists of the fact that stimuli from the outside provoke the strengthening of certain synapses, and the weakening of others.

Thus, the synaptic plasticity, cerebral or neuronal, allows the neurons to function correctly, communicate among themselves and modulate their activity according to the environment and the stimuli of the environment. In short, it allows the brain to adapt to changes and also enables its functions to be maximised.

One type of ionotropic receptor

At the structural and functional level, NMDA receptors, also called NMDAr, are ionotropic receptors . But let’s go back a bit; there are three types of brain receptors: ionotropes (as NMDA receptors are), metabotropes and self-receivers. 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 receiver itself acts as a channel.

Functions

NMDA receptors, along with glutamate, are related to a multitude of functions of the nervous system (NS). They are mainly responsible for regulating the post-synaptic excitatory potential of 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 migration processes.

1. Neural (or synaptic) plasticity

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

This is all due to neuronal plasticity, which is largely dependent 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

2. Memory

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

3. Learning

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

Bibliographic references:

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  • Morgado, I. (2005). Psychobiology of learning and memory: foundations and recent advances. Rev Neurol, 40 (5): 289-297.
  • Rosenweig, M.R., Breedlove, S.M & Watson, N.V. (2005). Psychobiology: an introduction to behavioural, cognitive and clinical neuroscience. Barcelona: Ariel.
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  • 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.