Document Type
Article
Publication Date
11-2022
Publisher
The Royal Society
Source Publication
Proceedings of the Royal Society B: Biological Sciences
Source ISSN
0962-8452
Original Item ID
DOI: 10.1098/rspb.2022.1565
Abstract
In the conventional model of serotonin neurotransmission, serotonin released by neurons in the midbrain raphe nuclei exerts its actions on forebrain neurons by interacting with a large family of post-synaptic receptors. The actions of serotonin are terminated by active transport of serotonin back into the releasing neuron, which is mediated by the serotonin reuptake transporter (SERT). Because SERT is expressed pre-synaptically and is widely thought to be the only serotonin transporter in the forebrain, the conventional model does not include serotonin transport into post-synaptic neurons. However, a large body of evidence accumulating since the 1970s has shown that serotonin, despite having a positive charge, can cross cell membranes through a diffusion-like process. Multiple low-affinity, high-capacity, sodium-independent transporters, widely expressed in the brain, allow the carrier-mediated diffusion of serotonin into forebrain neurons. The amount of serotonin crossing cell membranes through this mechanism under physiological conditions is considerable. Most prominent textbooks fail to include this alternative method of serotonin uptake in the brain, and even most neuroscientists are unaware of it. This failure has limited our understanding of a key regulator of serotonergic neurotransmission, impeded research on the potential intracellular actions of serotonin in post-synaptic neurons and glial cells, and may have impeded our understanding of the mechanism by which antidepressant medications reduce depressive symptoms.
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Andrews, Paul W.; Bosyj, Catherine; Brenton, Luke; Green, Laura; Gasser, Paul J.; Lowry, Christopher A.; and Pickel, Virginia M., "All the Brain's a Stage for Serotonin: The Forgotten Story of Serotonin Diffusion across Cell Membranes" (2022). Biomedical Sciences Faculty Research and Publications. 254.
https://epublications.marquette.edu/biomedsci_fac/254
Comments
Published version. Proceedings of the Royal Society B: Biological Sciences, Vol. 289, No. 1986 (November 2022). DOI. © 2022 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License. Used with permission.