Subtyping Serotonergic Neurons

 SEROTONERGIC neurons are brain cells that produce the neurotransmitter serotonin, which is involved in the regulation of an individual’s mood, appetite, breathing rate, and body temperature. Scientists have recently identified a number of diverse subgroups of serotonergic neurons, and have learnt that the differences between the various types may be important in dysfunction and disease.

Following the identification of a specific subgroup of serotonergic neurons responsible for increasing breathing rate in mice following the excessive build-up of CO2, Dr Susan Dymecki, Professor of Genetics, Harvard Medical School, Boston, Massachusetts, USA, and colleagues have tried to systematically characterise serotonergic neurons at the molecular level into a full set of subtypes. By completing a cross-disciplinary series of experiments, the research team have so far found that there are at least six major molecular subtypes of serotonergic neurons, which are defined by distinct gene expression patterns, and believe that the subtypes moderate different processes in the body. The researchers also report that the subtypes vary in other properties, including their developmental lineage, anatomical distribution, cell surface receptor composition, and electrical firing properties.

It is thought that the diversity of serotonergic neurons may help to explain how they are able to collectively perform so many distinct functions. Dr Dymecki commented: “To have the list of molecular players that make each of these subtypes different from one another gives us an important handle on learning more about what that cell type does and how we can manipulate only that subtype. It holds enormous therapeutic potential.” The research team also demonstrated that the gene expression and function of a serotonergic neuron depend on its cellular ancestor in the developing brain, in addition to its location in the adult brain stem, and that the molecular phenotypes of neurons remain tightly linked to their developmental origin.

Prof Dymecki’s team believe that, although the work was performed in mice, it will be possible to replicate their findings in humans because the serotonergic neuronal system is a highly conserved region of the brain across vertebrate species. It is hoped that further research could ultimately reveal the contributions of the serotonergic neuronal system to diseases such as autism, and lead to the development of more targeted therapies and biomarkers.


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