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 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 in our brain are capable of generating the torrents of information that we call “mental processes”, but these molecules are also found on 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 muscle fibers to contract.

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 or not action potentials (electrical impulses that are produced in the cell membrane), activate postsynaptic receptors (receptors of postsynaptic cells or neurons) and open ion channels (proteins of the neuronal membranes that contain pores that when they open, they allow the passage of charge particles such as ions), whereas neuromodulators do not create action potentials but rather 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 in the nervous system and neurotransmitters and slow changes with neuromodulators. Similarly, the latency (that is, the 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. Furthermore, 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 50-mm vesicles. in diameter, but that of neuromodulators is that of large 120-mm vesicles. diameter.

Types of receivers

Neuroactive substances can bind 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. At metabotropic receptors, neuromodulators often bind.

There are also other types of receptors that 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, transmitter 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 located) as in the peripheral nervous system (the rest) and causes diseases such as myasthenia gravis (neuromuscular disease that is due to weakness of skeletal muscles) and muscle dystonia (disorder characterized by involuntary twisting movements).

2. Biogenic amines

The biogenic amines are serotonin and catecholamines (epinephrine, norepinephrine, and dopamine) and act primarily through metabotropic receptors.

  • The Serotonin is synthesized from the raphe nuclei (brainstem); norepinephrine at the locus coeruleus (in the brain stem) and dopamine in the substantia nigra and ventral tegmental area (from where projections are sent to various regions of the anterior brain).
  • The dopamine (DA) is associated with pleasure and mood. A deficiency of this in the substantia nigra (portion of the midbrain and a fundamental element in the basal ganglia) produces Parkinson’s and the excess produces schizophrenia.
  • The noradrenaline is synthesized from dopamine, is related mechanisms fight and flight and causes deficit ADHD and depression.
  • The  adrenaline is synthesized from noradrenaline in the adrenal capsules or adrenal medulla, activates the sympathetic nervous system (system responsible for the innervation of smooth muscle, cardiac muscle and glands), participates in reactions fight and flight, increases heart rate and constricts blood vessels; 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 regulating emotional states and mental activity.

3. Transmitting amino acids

The most important excitatory transmitter 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 synapses in the CNS, where they bind to ionotropic receptors.

4. Neuropeptides

Neuropeptides are formed by amino acids and act primarily 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, and this is why some of these substances are used as therapeutic tools. in the treatment of psychopathological disorders and neurodegenerative diseases.

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