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. 2010;12(4):471-87.
doi: 10.31887/DCNS.2010.12.4/ycharnay.

Brain serotonergic circuitries

Yves Charnay  1 , Lucienne Léger
Affiliations

Brain serotonergic circuitries

Yves Charnay et al. Dialogues Clin Neurosci. 2010.

Abstract
in English, Spanish, French

Brain serotonergic circuitries interact with other neurotransmitter systems on a multitude of different molecular levels. In humans, as in other mammalian species, serotonin (5-HT) plays a modulatory role in almost every physiological function. Furthermore, serotonergic dysfunction is thought to be implicated in several psychiatric and neurodegenerative disorders. We describe the neuroanatomy and neurochemistry of brain serotonergic circuitries. The contribution of emergent in vivo imaging methods to the regional localization of binding site receptors and certain aspects of their functional connectivity in correlation to behavior is also discussed. 5-HT cell bodies, mainly localized in the raphe nuclei, send axons to almost every brain region. It is argued that the specificity of the local chemocommunication between 5-HT and other neuronal elements mainly depends on mechanisms regulating the extracellular concentration of 5-HT the diversity of high-affinity membrane receptors, and their specific transduction modalities.

Los circuitos serotoninérgicos cerebrales interactúan con otros sistemas de neurotransmisión en una infinidad de diferentes niveles moleculares. En humanos, como también en otras especies de mamíferos, la serotonina (5HT) tiene un papel modulador en casi todas las funciones fisiológicas. Además se postula que la disfunción serotoninérgica participa en diversos trastornos psiquiátricos y neurodegenerativos. Se describe la neuroanatomía y la neuroquímica de los circuitos serotoninérgicos cerebrales. También se discute la contribución de novedosos métodos de imágenes in vivo para la localización regional de sitios de unión de receptores y ciertos aspectos de su conectividad funcional en relación con la conducta. Los cuerpos de 5-HT, localizados principalmente en los núcleos del rafe, envían axones a casi todas las regiones cerebrales. Se argumenta que la especificidad de la comunicación química local entre 5-HT y otros elementos neuronales depende principalmente de mecanismos que regulan la concentración extracelular de 5-HT, de la diversidad de receptores de membrana de alta afinidad y de sus modalidades de transducción específicas.

Les circuits sérotoninergiques centraux sont le théâtre d'une myriade d'interactions moléculaires dévolues à leur communication. Chez l'homme comme chez les autres espèces, la sérotonine (5-HT) joue un rôle modulateur dans la presque totalité des fonctions physiologiques. De plus, un dysfonctionnement des systèmes sérotoninergiques est présumé impliqué dans diverses pathologies psychiatriques et neurodégénératives. Nous décrivons en détail les circuits sérotoninergiques centraux à partir d'études neuroanatomiques postmortem. La contribution des approches modernes in vivo permettant la localisation régionale de récepteurs et certains aspects de leur fonctionnalité corrélée à des comportements sont aussi discutées. Les corps cellulaires à 5-HT principalement localisés dans les noyaux des raphés projettent des axones dans la plupart des régions du cerveau. Ainsi la spécificité de la communication chimique locale établie entre les éléments neuronaux à 5-HT et les autres dépend de mécanismes régulant la concentration extracellulaire en 5-HT, de la diversité des récepteurs membranaires de haute affinité et de leurs modalités de transduction.

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Figures

Figure 1.
Figure 1.. Schematic sagittal view of the human brain showing the distribution of the serotonergic systems. The raphe nuclei containing the majority of the serotonergic cell bodies appear in purple. It is readily seen that these nuclei are exclusively located in the brain stem. The axons issued from them are drawn in red. The trajectories and extensive branching of the axons until the main terminal areas are illustrated. The densities of the serotonergic axonal networks in these terminal areas are given by the colored boxes. X, dorsal motor n of the vagus nerve; ACN, accumbens n; Amy, amygdala; cc, corpus callosum; Ce, cerebellum; CPu, caudate-putamen; Cx, cortex; DH, dorsal horn spinal cord; DRN, dorsa raphe n; Fcx, frontal cortex; Hip, hippocampus; Hyp, hypothalamus; IPN, interpeduncular n; LC, locus coeruleus; LS, lateral septum; MRN, median raphe n; n, nucleus; NTS, n of the solitary tract; OB, olfactory bulb; PAG, periaqueductal gray; RMg, raphe magnus n; RO, raphe obscurus n; Rpa, raphe pallidus; RPo, raphe pontis n; SN, subtantia nigra; Tha, thalamus; VH, ventral horn; VTA, ventral tegmental area Adapted from ref 129: Nieuwenhuis R. Monoamines: Chemoarchitecture of the Brain. Berlin, Germany: Springer Verlag; 1985:33-41. Copyright © Springer Verlag, 1985
Figure 2.
Figure 2.. The serotonergic neurotransmission depends on serotonin (5-HT) levels present in the extracellular space and on membrane receptors triggering functional changes in neighbouring neuronal elements. 5-HT synthesis, release and reuptake are regulated by several mechanisms including feedback inhibition by 5-HT1A, 5-HT1B/1D autoreceptors and a-2 adrenoceptors. Other mechanisms of regulation are receptor dimerization and desensitization affecting their trafficking and functionality. See text for further details.
Figure 3.
Figure 3.. Photographs illustrating the different scales provided by the different anatomical methods used to investigate the brain. In vivo imaging allows regional analyses (from the whole brain to groups of neurons), whereas electron microscopy provides images of neuronal cell bodies and is particularly useful to visualize axonal varicosities and their contacts with neighboring elements. In between are autoradiography in situ hybridization, and immunohistochemistry. DRN, dorsal raphe nucleus
See this image and copyright information in PMC

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