Neurotransmitters are endogenous chemicals that enable communication within the nervous system and between the nervous system and the rest of the body. They relay information between individual neurons, and ultimately regulate a wide range of bodily functions. There are various classes of neurotransmitters, with different functions and mechanisms of action. Neurotransmitter levels and function are crucial to maintaining homeostasis, and if altered can lead to diseases. Here we will discuss their mechanism of action, different classes and their clinical relevance. Pro Feature - 3D Model You've Discovered a Pro Feature Access our 3D Model Library Explore, cut, dissect, annotate and manipulate our 3D models to visualise anatomy in a dynamic, interactive way. Learn More Mechanism of Action Neurotransmitters transmit signals across a synapse at various locations, such as: From one neuron to another target neuron At the neuromuscular junction (NMJ), that is from a neuron to a target muscle cell From a neuron to a target gland. A synapse is a junction through which a neuron relays information to another neuron; it has three main components: The axon terminal (pre-synaptic side), where information is transmitted from The synaptic cleft The dendrite (post-synaptic side), receiving the information There is generally a low-level baseline level of neurotransmitter release that occurs without any need for stimulation. However, the amount released is increased in response to threshold action potentials. The binding of neurotransmitters to the post-synaptic neuron then results in either excitation or inhibition depending on which is released and the receptor it binds to. Some neurotransmitters also have a neuromodulatory action. These can act on large numbers of neurons at once and are involved in larger-scale regulation of groups of neurons. This process takes place over a much slower time course than excitatory and inhibitory transmission. vectorization: Mouagip (talk)Synapse_diag1.png: Drawn by fr:Utilisateur:DakeCorrections of original PNG by en:User:Nrets This W3C-unspecified vector image was created with Adobe Illustrator., CC BY-SA 3.0 <http://creativecommons.org/licenses/by-sa/3.0/>, via Wikimedia CommonsFig 1Diagram showing the basic model of neurotransmission. (A) Presynaptic neuron. (B) Postsynaptic neuron. (1) Mitochondria. (2) Synaptic vesicles containing neurotransmitters. (3) Autoreceptor. (4) Synaptic cleft. (5) Neurotransmitter receptor. (6) Calcium channel. (7) Fused vesicle releasing neurotransmitter. (8) Neurotransmitter reuptake pump. Neurotransmitters Classes of Neurotransmitter There are hundreds of neurotransmitters, but they can be grouped into classes depending on their structure, or function. Focusing on structure, neurotransmitters can be classed as: Monoamines – such as dopamine, noradrenaline, adrenaline, histamine, serotonin Amino acids – such as glutamate, GABA (gamma-aminobutyric acid), glycine, aspartate, D-serine Peptides – such as opioids, endorphins, somatostatin, oxytocin, vasopressin Other – such as acetylcholine (ACh), adenosine, nitric oxide Often, it is more useful to classify neurotransmitters based on their function: Excitatory neurotransmitters increase electrical excitability on the post-synaptic side through modulation of the trans-membrane ion flow to facilitate the transmission of an action potential. Inhibitory neurotransmitters decrease electrical excitability on the post-synaptic side to prevent the propagation of an action potential. Neuromodulators function to alter the strength of transmission between neurons by affecting the amount of neurotransmitter that is produced and released Specific Neurotransmitter Examples Glutamate Glutamate is typically synthesised within neurons from glutamine and is the most abundant neurotransmitter in the brain. It is an excitatory neurotransmitter and binds to four different receptors: NMDA receptors – an ionotropic receptor permeable to sodium, potassium, and calcium ions AMPA receptors – an ionotropic receptor permeable to sodium and potassium ions Kainate receptors – an ionotropic receptor permeable to sodium and potassium ions, these are similar to AMPA receptors but much less common Metabotropic G-protein coupled receptors It is thought to have an essential role in learning and memory, particularly in the process of long-term potentiation. Clavecin, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons Fig 2The chemical structure of glutamate. Acetylcholine (ACh) ACh is used both in the central and peripheral nervous system, in particular at the NMJ. It is synthesised in neurons from choline and acetyl-CoA. ACh is an excitatory neurotransmitter and binds to two different receptor types: Nicotinic ACh receptors (nAChRs) – iontropic receptors found at the NMJ, within the CNS and the sympathetic and parasympathetic nervous system. They are also found pre-synaptically in the brain and are thought to have a neuromodulatory effect Muscarinic ACh receptors (mAChRs) – G protein coupled receptors found in the CNS and within post-ganglionic parasympathetic neurons Because it is present in so many different areas of the body ACh plays a role in many different processes, including stimulation of muscles at the NMJ; arousal; attention; digestion and salivation. NeuroFall2021, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons Fig 3The chemical structure of Acetylcholine. GABA GABA is synthesised from glutamate and is an inhibitory neurotransmitter within the CNS. It binds to two different receptors: GABA A receptors – ionotropic receptors permeable to chloride and bicarbonate ions GABA B receptors – metabotropic G protein-coupled receptors GABA has both rapid inhibitory effects when binding to post-synaptic receptors and slower inhibition via neuromodulation at pre-synaptic receptors. It is involved in many different processes in the brain, such as regulating neuronal activity; anxiety, and sleep. Glycine Glycine is an amino acid that is used at the majority of inhibitory synapses in the spinal cord and brainstem. It binds to ionotropic receptors which are permeable to chloride and bicarbonate ions. As an inhibitory neurotransmitter glycine is important in many motor and sensory functions, such as reciprocal inhibition of antagonistic muscles in spinal reflexes. Glycine also has an excitatory role within the CNS as it is a co-agonist at glutamatergic NMDA receptors. Clavecin, CC BY-SA 4.0 <https://creativecommons.org/licenses/by-sa/4.0>, via Wikimedia Commons Fig 4The chemical structure of glycine. Clinical Relevance Benzodiazepines and GABA Transmission Benzodiazepines are a class of drugs typically prescribed for their anxiolytic and sedative properties. Examples include; chlordiazepoxide, clonazepam, diazepam and lorazepam. They do not act directly on receptors but instead bind allosterically to GABA receptors. This results in an increased probability of the channel opening and potentiation of GABAergic neurotransmission within the brain. Benzodiazepines are prescribed for a variety of conditions, such as insomnia, anxiety disorders, seizures, and alcohol withdrawal. However, they can have a number of adverse effects including memory loss; increased likelihood of falls in the elderly, and nausea. They also have the potential to be addictive and so are generally only prescribed for short-term use. Do you think you’re ready? Take the quiz below Pro Feature - Quiz Neurotransmitters Question 1 of 3 Submitting... Skip Next Rate question: You scored 0% Skipped: 0/3 More Questions Available Upgrade to TeachMePhysiology Pro Challenge yourself with over 1800 multiple-choice questions to reinforce learning Learn More Print Article Rate This Article