Neurotransmitters and neuromodulators: how do they work?
It can be said that in all neurons there is a way of communicating between them called synapses.
At synapses, neurons communicate with each other through neurotransmitters , which are molecules responsible for sending signals from one neuron to the next. Other particles called neuromodulators also intervene in the communication between nerve cells
Thanks to neurotransmitters and neuromodulators, the neurons of our brain are capable of generating the torrents of information that we call "mental processes" , but these molecules are also found in the periphery of the nervous system, in the synaptic terminals of the 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 another as a neuromodulator.
Hence their difference: neurotransmitters create or not action potentials (electrical impulses that occur in the cell membrane), activate postsynaptic receptors (receptors of postsynaptic cells or neurons) and open ion channels (proteins of neuronal membranes containing pores that when they open, they allow the passage of charge particles like ions) while the neuromodulators do not create action potentials but rather regulate the activity of the ion channels.
In addition, neuromodulators modulate the efficiency of the membrane potentials of postsynaptic cells produced in the receptors associated with ion channels. This is produced by the activation of G proteins (particles that carry information from a receptor to the effector proteins). A neurotransmitter opens a channel, whereas a neuromodulator affects one or two dozens of 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. Likewise, the latency (that is, the changes in the postsynaptic membrane potential due to the effect of a neurotransmitter) of the neurotransmitters is 0.5-1 milliseconds, whereas that of the neuromodulators is several seconds. In addition, the "life expectancy" of neurotransmitters is 10-100 ms. and that of neuromodulators is from minutes to hours.
Regarding 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. diameter.
Types of receivers
Neuroactive substances can be linked to two types of receptors, which are the following:
Ionotropic receptors
They are receptors that open ion channels . In most, neurotransmitters are found.
Metabotropic receptors
Receptors bound to G proteins . Neuromodulators usually join metabotropic receptors.
There are also other types of receptors that are the autoreceptors or presynaptic receptors that participate in the synthesis of the substance released in 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.
Neurotransmitter classes
The neurotransmitters are classified into groups: acetylcholine, biogenic amines, transmitting amino acids and neuropeptides.
1. Acetylcholine
Acetylcholine (ACh) is the neurotransmitter of the neuromuscular junction , it is synthesized in the septal nuclei and nasal nuclei of Meynert (nuclei of the anterior brain), it can be both in the central nervous system (where the brain and spinal cord are) and in the peripheral nervous system (the rest) and causes diseases such as myasthenia gravis (neuromuscular disease due to skeletal muscle weakness) and muscle dystonia (disorder characterized by involuntary twisting movements).
2. Biogenic amines
The biogenic amines are serotonin and catecholamines (adrenaline, noradrenaline and dopamine) and they act mainly by 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 which projections are sent to various regions of the anterior brain).
- Dopamine (DA) is related to pleasure and mood.A deficit of this in the substantia nigra (midbrain portion and fundamental element in the basal ganglia) produces Parkinson's and the excess produces schizophrenia.
- Noradrenaline is synthesized from dopamine, is related to fight and flight mechanisms and a deficit causes ADHD and depression.
- Adrenaline is synthesized from noradrenaline in the adrenal or adrenal medulla, activates the sympathetic nervous system (system responsible for the innervation of smooth muscles, heart muscle and glands), participates in fight and flight reactions, increases heart rate and contracts blood vessels; It produces emotional activation and is related to stress pathologies and general adaptation syndrome (a syndrome that involves subjecting the body to stress).
- The biogenic amines They play important roles in the regulation of affective states and mental activity.
3. Transmitting amino acids
The most important excitatory transmitting amino acids are glutamate and aspartate and the inhibitors 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 by 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 the modification of the efficiency with which chemical nerve communication occurs, and this is why some of these substances are used as therapeutic tools in the treatment of psychopathological disorders and neurodegenerative diseases.
