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Embracing diversity in the 5-HT neuronal system
Benjamin W Okaty1, Kathryn G Commons2, Susan M Dymecki3
1Department of Genetics, Harvard Medical School, Boston, MA, USA. bokaty@genetics.med.harvard.edu.
Nature Reviews. Neuroscience
|April 6, 2019
Summary
Serotonin (5-HT) neurons exhibit significant diversity, suggesting distinct subtypes. Recent molecular and functional data support a reframing of the serotonin system, paving the way for targeted therapies for related disorders.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Neurons synthesizing serotonin (5-hydroxytryptamine, 5-HT) share a core genetic program for their phenotype.
- Despite this shared identity, 5-HT neurons display considerable heterogeneity in anatomy, morphology, connectivity, electrophysiology, and gene expression.
- This diversity implies the existence of functionally distinct subtypes of 5-HT neurons, but their specific functions have been difficult to ascertain.
Purpose of the Study:
- To re-evaluate the organization of the 5-HT neuronal system.
- To integrate recent molecular, genomic, and functional data with classical findings.
- To propose a new framework for understanding 5-HT neuron diversity and its therapeutic implications.
Main Methods:
- Review and synthesis of molecular genetic data.
- Analysis of genomic studies.
- Integration of functional neurobiological findings.
- Consideration of classical neuroanatomical and physiological studies.
Main Results:
- The 5-HT system is not monolithic but comprises diverse subsystems.
- Differential gene expression supports co-transmission of additional neurotransmitters in specific 5-HT neuron populations.
- Recent data provide a more nuanced view of 5-HT neuron heterogeneity.
Conclusions:
- The 5-HT system is best understood as a conglomeration of diverse subsystems.
- Recognizing this diversity is crucial for understanding brain function and dysfunction.
- This reframing can inspire novel, targeted therapeutic strategies for clinically distinct 5-HT-related disorders.
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