NMDA receptors of the nervous system: what are they and what functions do 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 will talk about one of them: NMDA receptors.

In this article we will learn what these types of receptors consist of, what characteristics they present, 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.

• Related article: "Types of neurotransmitters: functions and classification"

What are neurotransmitters and how are they classified?

Neurotransmitters are biomolecules that enable the transmission of information between neurons. (that is, 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 the one that divides them into three large groups:

1. amines

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

2. Amino acids

include the glutamate, GABA, glycine and histamine.

3. Neuropeptides

For their part, 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 in the brain par excellence., 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 the cells (for example in neurons) where neurotransmitters bind, allowing the synapse (which can be electrical or chemistry).

To understand it in a simple way and, broadly speaking, synapses are those connections between neurons that keep these nerve cells in constant communication and that allow the transmission of information, which enables the achievement of different processes: thinking, making decisions, paying attention, reasoning, speaking...

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

NMDA receptors: general characteristics

NMDA receptors are highly complex proteins that act as glutamate receptors. At a functional level, NMDA receptors, along with AMPA glutamate receptors, are fundamentally related to two cognitive processes: learning and memory. Specifically, NMDA receptors are essential, above all, for memory. Besides, they are also strongly linked to neural or synaptic plasticity.

On the other hand, NMDA receptors have also been related 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 or stroke.

• You may be interested in: "What is the synaptic gap and how does it work?"

Functioning

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

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

The flow of calcium ions, specifically, is essential to enhance the processes of synaptic plasticity or brain plasticity. This type of plasticity consists in the fact that external stimuli cause the strengthening of certain synapses, and the weakening of others.

Thus, synaptic plasticity, cerebral or neuronal, allows neurons to function correctly, communicate with each other and modulate their activity according to the environment and the 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

At a structural and functional level, NMDA receptors, also called NMDAr, are ionotropic receptors. But let's back up a bit; 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 characteristic is that they function as specific ionic channels for certain ions, that is, the receptor itself acts as a channel.

functions

NMDA receptors, together with glutamate, are related to a multitude of functions of the nervous system (NS). They are mainly responsible for regulating the postsynaptic 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 played by glutamate binding to NMDA receptors in cell migration processes.

1. Neuronal (or synaptic) plasticity

Neuronal plasticity and its relationship with NMDA receptors has been widely 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 SN circuits, that is, they promote their functional connections.

All this occurs thanks to neuronal plasticity, which depends largely 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

Regarding its link with memory, NMDA receptors have been shown to 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 lived experiences and that configures our autobiography).

• You may be interested in: "Types of memory: how does the human brain store memories?"

3. Learning

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

Bibliographic 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.