What is Neuromodulation?

Neuromodulation is the process by which nervous activity is regulated by way of controlling the physiological levels of several classes of neurotransmitters.

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Neuromodulators are a subset of neurotransmitter. Unlike neurotransmitters, the release of neuromodulators occurs in a diffuse manner (“volume transmission”). This means that an entire neural tissue may be subject to the neuromodulator’s action due to exposure. This, in turn, can tune the neural circuitry of an entire brain region; not just that of an individual neuron.

This is in contrast with the release of a neurotransmitter, which occurs at a specific synapse during direct synaptic transmission. Furthermore, neuromodulators and neurotransmitters act on different types of neuroreceptors.

While neurotransmitters target fast-acting "ionic" neuroreceptors that convey electrochemical signals into the target neuron, neuromodulators target the slower G-protein neuroreceptors (of which there are three types).

Importantly, the act of neuromodulation, unlike that of neurotransmission, does not necessarily carry excitation of inhibition from one neuron to another but instead alters either the cellular or synaptic properties of certain neurons so that neurotransmission between them is changed.


Some examples of neuromodulators are highlighted below:

Noradrenaline (Noradrenaline system)

Noradrenaline regulates the activity of both neuronal and non-neuronal cells. It participates in the rapid modulation of cortical circuits and cellular energy metabolism, and on a slower time scale in inflammation and neuroplasticity.

Of the multiple sources of NA in the brain, the locus coeruleus plays a major role in noradrenergic signaling. A substantial amount of evidence has demonstrated that this neuromodulator plays a critical role in modulating plasticity, learning and memory via the hippocampus within the brain.

Dopamine (Dopamine system)

Dopamine is centrally involved in reward, approach behavior, exploration, and various aspects of cognition. Variations in this neuromodulator function appear to be associated with variations in personality. This results in changes in relatively stable patterns of behavior, motivation, emotion, and cognition that differ among individuals. No concrete evidence exists concerning its role in personality, and it has been implicated in traits ranging from extraversion to aggression to intelligence to schizotypy.

Serotonin (Serotonin system)

Over 90% of the body's serotonin is found in the gastrointestinal tract where it has a role in regulating bowel function and movements. It also plays a part in reducing the appetite while consuming a meal.

With this said, it is most well-known for its role in the brain where it plays a major part in mood, anxiety and happiness.

Acetylcholine (Cholinergic system)

Acetylcholine (Ach) has a role in the control of autonomic functions but it is likely that it also modulates adaptive responses to environmental and metabolic conditions. Cholinergic signaling can influence thermoregulation, sleep patterns, food intake and endocrine functions including pancreatic insulin and glucagon release.

The hypothalamus is vital in homeostatic responses regulating metabolism, therefore modulation of hypothalamic function by ACh is likely to be important in adaptation to peripheral autonomic signals to the brain. ACh signaling in a number of brain areas might also be important for stress responses as several studies have shown that stress increases its release in a brain region-specific manner.

Pharmacological applications of neuromodulation

  • Sympathomimetic and sympatholytic drugs: these enhance and block at least some of the effects of noradrenaline released by the sympathetic nervous system, respectively.
  • Dopamine reuptake inhibitors: these prevent dopamine reuptake by blocking the action of the dopamine transporter. These drugs are frequently used in the treatment of conditions including ADHD, depression and narcolepsy.
  • Selective serotonin reuptake inhibitors: these temporarily prevent the removal of serotonin from specific synapses, thereby enhancing the effect of released serotonin. These are used in treating depression.
  • Cholinesterase inhibitors: these bind to cholinesterase resulting in increased acetylcholine in the synapses. These are used to treat dementia in patients with Alzheimer's disease.

Neuromodulation is also a category of treatment that involves stimulation or direct administration of medications to the body’s nervous system for therapeutic purposes. This aims to modulate the activity of target cells as an approach to pain control and neurological dysfunction by treating movement disorders, conditions such as spasticity and epilepsy, as well as pain syndromes.

Spinal cord stimulation

This common form of neuromodulation involves using a device to deliver electrical current in therapeutic doses to the spinal cord to disrupt pain signals from the spinal cord to the brain, converting them to a more pleasant tingling sensation. This has been proven a safe and effective therapeutic approach for managing chronic pain of the arms and legs, neck and back often after spine surgery, or for other neuropathic conditions.


Further Reading

Last Updated: May 10, 2021

Afsaneh Khetrapal

Written by

Afsaneh Khetrapal

Afsaneh graduated from Warwick University with a First class honours degree in Biomedical science. During her time here her love for neuroscience and scientific journalism only grew and have now steered her into a career with the journal, Scientific Reports under Springer Nature. Of course, she isn’t always immersed in all things science and literary; her free time involves a lot of oil painting and beach-side walks too.


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