blue colored neural network

Neurotransmitters VS Neuromodulators

On this page, I will explain what a neurotransmitter is, what a neuromodulator is, and the differences between them.

What is a Neurotransmitter?

neurotransmission between presynapse and post synapse
By OpenStax [CC BY 4.0], via Wikimedia Commons
A neurotransmitter is a chemical messenger released from the nerve ending of a neuron to communicate with with adjacent neurons. The neurotransmitters are released by presynaptic neurons, and either excite or inhibit the post synaptic neuron.

After release, the neurotransmitters quickly degrade in the synaptic cleft. Or the neurotransmitters are taken back up (this is called “reuptake”) by the presynaptic neuron to limit the amount of time they are in the synaptic cleft- thus limiting the affect of the neurotransmitter.

If you prevent the reuptake of a neurotransmitter, you are increasing its affect on the post synaptic neurons. That’s the function of reuptake inhibitors, like SSRI (Selective Serotonin Reuptake Inhibitor) which increases the affect of serotonin on the brain.

Note that neurotransmitters bind to ionotropic receptors.

Examples of neurotransmitters: Acetylcholine, Dopamine, GABA, Glycine, Histamine, Norepinephrine and Serotonin.

What is a Neuromodulator?

A neuromodulator is a chemical messenger released from a neuron in the central nervous system, or in the periphery, that affects a diverse population of neurons that has the appropriate receptor. This large range of influence contrasts with neurotransmitters, which has only one presynaptic neuron directly influencing a single postsynaptic neuron connected to it.

Neuromodulators contoll how “loudly” neurons communicate with each other

But to be more specific, the function of neuromodulatorsis to alter the strength of signal transmissions between neurons. Nueromodulators can alter neuronal signal transmission by controlling the amount of neurotransmitters synthesized and released by the neurons.

The release of neuromodulators may influence the neurons near the site or release, or may affect neurons quite far from the site of release. This means that neuromodulators have a very long range of action compared to regular neurotransmitters.

The fact that neuromodulators can have an affect far from its location of release also means that its distinction with a neurohormone can become very blurred.

Finally, I would like to mention that neuromodulators are longer-lasting than regular neurotransmitters. I believe this is due to the fact that neuromodulators aren’t reabsorbed by their presynaptic neuron.

Note that neuromodulators bind to metabotropic receptors. Metabotropic receptors have a slow-acting effect, sensitizing or desensitizing neurons by changing the strength of signal transmission between neurons. I mentioned this before.

Examples of neuromodulators: opioid peptides such as enkephalins, endorphins, dynorphins.

Examples of Neuromodulators that are also neurotransmitters: acetylcholine, dopamine, histamine, norepinephrine, serotonin and octopamine.

You should be noticing a pattern now. Many chemical messengers that are neurotransmitters also act as a neuromodulators.

Neurotransmitter vs Neuromodulator

ionic metabotropic receptors diagram
By OpenStax [CC BY 4.0], via Wikimedia Commons Notice that ionotropic receptors have a direct effect, whereas metabotropic receptors have an indirect effect that occurs gradually.
A neuromodulator is a type of neurotransmitter.

The three main things distinguish neuromodulators as a subclass:

1. They are released “diffusely” via “volume transmission”, that is, the neurotransmitter is generally released into the neural tissue and not at a specific synapse, so it functions more as a chemical broadcast signal to a (possibly small) brain region rather than being targeted at particular neurons.

2. They generally use a different different type of neuroreceptor. The targeted, synaptically-released neurotransmitters use fast-acting “ionic” neuroreceptors that transmit positive (+) and negative (-) electrical signals into the target neuron. Neuromodulators, however, use so-called “metabotropic” or “G-protein” neuroreceptors of three types: Gs, Gi, and Gq. These are slow-acting receptors that tune and modulate the functioning of the neuron over longer periods.

3. There are specific neurotransmitters that have been categorized as neuromodulators because they almost always work in the way described by #1 and #2. Those are: dopamine (D receptors), serotonin (5HT receptors), acetylcholine (M and nicotinic receptors), noradrenaline (alpha and beta receptors), and histamine (H receptors). These neurotransmitters tune the functioning of neural circuits in neural tissue rather than sending signals directly into particular neurons.[1]

Receptor Makes the Difference

The kind of receptor the chemical interacts with determines whether its considered a neurotansmitter or a neuromodulator.

Because the receptor is what matters,  the same chemical can be both a fast-acting neurotransmitter and a slow-acting neuromodulator. In some cases, the same chemical can have  both effects on the same postsynaptic cell simultaneously.

What is a Neurohormone?

A neurohormone is a chemical messenger that is released by neuroendocrine cells. Neuroendocrine cells are cells that receive an input from neurons like neurotransmitters, and in response output or release messenger molecules (a.k.a. hormones) into the blood stream.

By releasing the hormones into the blood stream, neurohormones can exert its effect on very distant peripheral targets. Neurohormones differ from neuromodulator in the extent of their actions.

So an example of neuroendocrine cell is the cells of the adrenal medulla, which is the innermost part of the adrenal gland. The adrenal medulla releases adrenaline into the blood stream in response to stimulation by the sympathetic preganglionic neurons, which are neurons from the autonomic nervous system.

You should also note that hormones last up to 10 times longer than neurotransmitters

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  1. What is the difference between neurotransmitters and neuromodulators? [Quora]

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