Neuromodulation

In neuroscience, neuromodulation is the process in which several classes of neurotransmitters in the nervous system regulate diverse populations of neurons. As opposed to direct synaptic transmission in which one presynaptic neuron directly influences a postsynaptic partner, neuromodulatory transmitters secreted by a small group of neurons diffuse through large areas of the nervous system, having an effect on multiple neurons. Examples of neuromodulators include dopamine, serotonin, acetylcholine, histamine and others.

A neuromodulator is a relatively new concept in the field and it can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the CSF (cerebrospinal fluid) and influencing (or modulating) the overall activity level of the brain. For this reason, some neurotransmitters are also considered as neuromodulators. Examples of neuromodulators in this category are serotonin and acetylcholine

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Neuromuscular systems

Neuromodulators may alter the output of a physiological system by acting on the associated inputs (for instance, central pattern generators). However, modeling work suggests that this alone is insufficient^[1], because the neuromuscular transformation from neural input to muscular output may be tuned for particular ranges of input. Stern et al. (2007) suggest that neuromodulators must act not only on the input system but must change the transformation itself to produce the proper contractions of muscles as output.^[1]

Diffuse modulatory neurotransmitter systems

Neurotransmitter systems are systems of neurons in the brain expressing certain types of neurotransmitters, and thus form distinct systems. Activation of the system causes effects in large volumes of the brain, called volume transmission.

The major neurotransmitter systems are the noradrenaline (norepinephrine) system, the dopamine system, the serotonin system and the cholinergic system. Drugs targetting the neurotransmitter of such systems affects the whole system, and explains the mode of action of many drugs.

Most other neurotransmitters, on the other hand, e.g. glutamate, GABA and glycine, are used very generally throughout the central nervous system.

Comparison

Noradrenaline system

Further reading: Norepinephrine#Norepinephrine_system

The noradrenaline system consists of just 1500 neurons on each side of the brain, which is diminutive compared to the total amount of more than 100 billion neurons in the brain. Nevertheless, when activated, the system plays major roles in the brain, as seen in table above. Noradrenaline is released from the neurons, and acts on adrenergic receptors.

Dopamine system

Further reading: Dopamine#Functions in the brain

The dopamine system consists of several pathways, originating from e.g. the substantia nigra. It acts on dopamine receptors.

Parkinson's disease is at least in part related to failure of dopaminergic cells in deep-brain nuclei, for example the substantia nigra. Treatments potentiating the effect of dopamine precursors have been proposed and effected, with moderate success.

Pharmacology

• Cocaine, for example, blocks the reuptake of dopamine, leaving these neurotransmitters in the synaptic gap longer.
• AMPT prevents the conversion of tyrosine to L-DOPA, the precursor to dopamine; reserpine prevents dopamine storage within vesicles; and deprenyl inhibits monoamine oxidase (MAO)-B and thus increases dopamine levels.

Serotonin system

Further reading: Serotonin#Gross anatomy

The serotonin system system contains only 1% of total body serotonin, the rest being found as transmitters in the peripheral nervous system. It travels around the brain along the medial forebrain bundle and acts on serotonin receptors. In the peripheral nervous system (such as in the gut wall) serotonin regulates vascular tone.

Pharmacology

• Prozac is a selective serotonin reuptake inhibitor (SSRI), hence potentiating the effect of naturally released serotonin.

Cholinergic system

Further reading: Acetylcholine#in CNS

The cholinergic system works primary by M1 receptors, but M2-, M3-, M4- and M5 receptors are also found in the CNS.

Others

The gamma-aminobutyric acid (GABA) system is more generally distributed throughout the brain. Nevertheless, it has an overall inhibitory effect.

• Opioid peptides - these substances block nerve impulse generation in the secondary afferent pain neurons. These peptides are called opioid peptides because they have opium-like activity. The types of opioid peptides are:
  • Endorphins
  • Enkephalins
  • Dynorphins
• Substance P
• Octopamine

Other uses

Neuromodulation also refers to a medical procedure used to alter nervous system function for relief of pain. It consists primarily of electrical stimulation, lesioning of specific regions of the nervous system, or infusion of substances into the cerebrospinal fluid. Electrical stimulation are devices such as Spinal Cord Stimulators (SCS) (surgically implanted) or Transcutaneous Electrical Nerve Stimulators (TENS) (external device).

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