Brain from top to bottom - Neurotransmitters

SYNAPSES Thanks to research by hundreds of laboratories throughout the world, the main entities involved in synaptic transmission have now been identified. They include over sixty neurotransmitters and hundreds of subtypes of receptors. Since a single neuron may release several different neurotransmitters at once, the soup of molecules and ions in the synaptic gap can be decoded only by means of very specific affinities between neurotransmitters and their receptors. A combination of neurotransmitters that can act on various subtypes of receptors can thus have varying effects, depending on what particular receptors they are acting upon. This diagram shows a synapse that is capable of long-term potentiation, a synaptic facilitation mechanism that is the basis for memory. The neurotransmitter involved here is glutamate. The enlarged diagram shows just three of the approximately twenty known subtypes of glutamate receptors. When glutamate binds to these receptors, it not only causes the ion channels to open but also triggers several cascades of chemical reactions, also represented in this diagram. Many of these reactions involve “second messengers:” molecules that relay signals from neurotransmitters within the postsynaptic neuron and that can in turn cause other ion channels to open or close. The effects of second messengers can extend all the way to the neuron’s nucleus, thus influencing its synthesis of new proteins, receptors, or channels, for example. Ion channels too are large proteins embedded in the neuronal membrane. It is the selective opening of all these various channels that, by changing the membrane’s electrical potential, produces the action potential. It is also these channels that let calcium ions enter the presynaptic neuron when the action potential reaches the axon’s terminal button–a crucial step that leads to the fusion of the synaptic vesicles with the membrane and their expulsion of neurotransmitters into the synaptic gap. Lastly, this overview of the entities involved in neurotransmission would not be complete without a mention of the other transmembrane proteins that reabsorb neurotransmitters into the presynaptic neuron or that actively pump ions through the membrane against their natural gradient.

	Many peptides act more as neuromodulators than as neurotransmitters. Neuromodulators are substances that do not propagate nerve impulses directly, but instead affect the synthesis, breakdown, or reabsorption (reuptake) of neurotransmitters. Neuromodulators can also exert regulatory effects on many extra-synaptic receptors, rather than on synaptic sites exclusively.		NEUROTRANSMITTERS To be considered a neurotransmitter, a molecule must meet several criteria. 1) It must be produced inside a neuron, found in the neuron’s terminal button, and released into the synaptic gap upon the arrival of an action potential. 2) It must produce an effect on the postsynaptic neuron. 3) After it has transmitted its signal to this neuron, it must be deactivated rapidly. 4) It must have the same effect on the postsynaptic neuron when applied experimentally as it does when secreted by a presynaptic neuron. Over 60 different molecules are currently known to meet these criteria. Among the small molecules constituting the “classical” neurotransmitters, the best known are: acetylcholine serotonin catecholamines, including epinephrine, norepinephrine, and dopamine excitatory amino acids such as aspartate and glutamate (half of the synapses in the central nervous system are glutamatergic) inhibitory amino acids such as glycine and gamma-aminobutyric acid (GABA; one-quarter to one-third of the synapses in the central nervous system are GABAergic) histamine adenosine adenosine triphosphate (ATP) Peptides form another large family of neurotransmitters, with over 50 known members. Here is a very partial list: substance P, beta endorphin, enkephalin, somatostatin, vasopressin, prolactin, angiotensin II, oxytocin, gastrin, cholecystokinin, thyrotropin, neuropeptide Y, insulin, glucagon, calcitonin, neurotensin, bradykinin. Certain soluble gases also act as neurotransmitters. The most important member of this category is nitrogen monoxide (NO). These neurotransmitters act by their own distinctive mechanism: they exit the transmitting neuron’s cell membrane by simple diffusion and penetrate the receiving neuron’s membrane in the same way.

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