Neurotransmitters and neuromodulators: how do they work?

We explain the basic functioning of synapses.

It can be said that in all neurons there is a way of communicating with each other called a synapse.

At synapses, neurons communicate with each other by means of neurotransmitters, which are molecules in charge of the communication between neurons.which are molecules responsible for sending signals from one neuron to the next. Other particles called neuromodulators are also involved in the communication between nerve cells.

Thanks to neurotransmitters and neuromodulators, the neurons of our brain are able to generate the torrents of information that we call "mental processes".However, these molecules are also found in the periphery of the nervous system, in the synaptic terminals of motor neurons (neurons of the central nervous system that project their axons to a muscle or gland), where they stimulate the muscle fibers to contract them.

Differences between neurotransmitter and neuromodulator

Two or more neuroactive substances can be in the same nerve terminal and one can function as a neurotransmitter and the other as a neuromodulator.

Hence their difference: neurotransmitters create action potentials (electrical impulses produced in the cell membrane), activate postsynaptic receptors (receptors of postsynaptic cells or neurons) and open ion channels (proteins in neuronal membranes containing pores that, when open, allow the passage of charged particles such as ions) whereas neuromodulators do not create action potentials but regulate the activity of ion channels.

In addition, neuromodulators modulate the efficacy of postsynaptic cell membrane potentials produced at ion channel-associated receptors. This occurs through the activation of G proteins (particles that carry information from a receptor to effector proteins). A neurotransmitter opens a channel, whereas a neuromodulator affects one or two dozen G proteins.which produce cAMP molecules, opening many ion channels at the same time.

There is a possible relationship of rapid changes of the nervous system and neurotransmitters and slow changes with neuromodulators. Similarly, the latency (i.e., changes in the postsynaptic membrane potential due to the effect of a neurotransmitter) of neurotransmitters is 0.5-1 milliseconds, whereas that of neuromodulators is several seconds. Moreover, the "life expectancy" of neurotransmitters is 10-100 ms and that of neuromodulators is minutes to hours.

As for the differences between neurotransmitters and neuromodulators according to their shape, that of neurotransmitters is similar to that of small vesicles of 50 mm in diameter, but that of neuromodulators is that of large vesicles of 120 mm in diameter.

Types of receptors

Neuroactive substances can bind to two types of receptors, which are as follows:

Ionotropic receptors

Ionotropic receptors are receptors that open ion channels. In most of them, neurotransmitters are found.

Metabotropic receptors

G protein-bound receptors. Metabotropic receptors usually bind neuromodulators.

There is also another type of receptors which are the autoreceptors or presynaptic receptors that participate in the synthesis of the substance released at the terminal. If there is excess release of the neuroactive substance, it binds to the autoreceptors and produces an inhibition of the synthesis avoiding the exhaustion of the system.

Classes of neurotransmitters

Neurotransmitters are classified into groups: acetylcholine, biogenic amines, amino acid transmitters and neuropeptides.

1. Acetylcholine

Acetylcholine (ACh) is the neurotransmitter of the neuromuscular junction.is synthesized in the septal nuclei and nasal nuclei of Meynert (nuclei of the anterior encephalon), can be both in the central nervous system (where the brain and spinal cord are located) and in the peripheral nervous system (the rest) and causes diseases such as myasthenia gravis (neuromuscular disease due to weakness of skeletal muscles) and muscular dystonia (disorder characterized by involuntary twisting movements).

2. Biogenic amines

The biogenic amines are serotonin and catecholamines (adrenaline, noradrenaline and dopamine) and act mainly through metabotropic receptors.

• Serotonin is synthesized from the raphe nuclei (in the brainstem); noradrenaline in the locus coeruleus (in the brainstem) and dopamine in the substantia nigra and ventral tegmental area (from where projections are sent to various regions of the forebrain).

• Dopamine (DA) is related to pleasure and mood. A deficit of it in the substantia nigra (a portion of the midbrain and a fundamental element in the basal ganglia) produces Parkinson's disease and an excess produces schizophrenia.

• Norepinephrine is synthesized from dopamine, it is related to fight and flight mechanisms and a deficit causes adhd and depression.

• Adrenaline is synthesized from noradrenaline in the adrenal capsules or adrenal medulla, activates the sympathetic nervous system (system responsible for the innervation of smooth muscles, cardiac muscle and glands), participates in fight and flight reactions, increases heart rate and constricts blood vessels; it produces emotional activation and is related to stress pathologies and general adaptation syndrome (syndrome that consists of subjecting the body to stress).

• The biogenic amines play important roles in the regulation of affective states and mental activity.

3. Transmitter amino acids

The most important excitatory transmitter amino acids are glutamate and aspartate and the inhibitory ones are GABA (gamma immunobutyric acid) and glycine. These neurotransmitters are distributed throughout the brain and participate in almost all CNS synapses, where they bind to ionotropic receptors.

4. Neuropeptides

Neuropeptides are formed from amino acids and act mainly as neuromodulators in the CNS.. The mechanisms of chemical synaptic transmission can be affected by psychoactive substances whose effect on the brain is to modify the efficiency with which chemical nerve communication occurs, which is why some of these substances are used as therapeutic tools in the treatment of psychopathological disorders and neurodegenerative diseases.