Conditional anterograde tracing reveals distinct targeting of individual serotonin cell groups (B5-B9) to the forebrain and brainstem.
Serotoninergic innervation of the central nervous system is provided by hindbrain raphe nuclei (B1-B9). The extent to which each raphe subdivision has distinct topographic organization of their projections is still unclear. We provide a comprehensive description of the main targets of the rostral serotonin (5-HT) raphe subgroups (B5-B9) in the mouse brain. Adeno-associated viruses that conditionally express GFP under the control of the 5-HT transporter promoter were used to label small groups of 5-HT neurons in the dorsal (B7d), ventral (B7v), lateral (B7l), and caudal (B6) subcomponents of the dorsal raphe (DR) nucleus as well as in the rostral and caudal parts of the median raphe (MR) nucleus (B8 and B5, respectively), and in the supralemniscal (B9) cell group. We illustrate the distinctive and largely non-overlapping projection areas of these cell groups: for instance, DR (B7) projects to basal parts of the forebrain, such as the amygdala, whereas MR (B8) is the main 5-HT source to the hippocampus, septum, and mesopontine tegmental nuclei. Distinct subsets of B7 have preferential brain targets: B7v is the main source of 5-HT for the cortex and amygdala while B7d innervates the hypothalamus. We reveal for the first time the target areas of the B9 cell group, demonstrating projections to the caudate, prefrontal cortex, substantia nigra, locus coeruleus and to the raphe cell groups. The broad topographic organization of the different raphe subnuclei is likely to underlie the different functional roles in which 5-HT has been implicated in the brain. The present mapping study could serve as the basis for genetically driven specific targeting of the different subcomponents of the mouse raphe system.
Inserm UMR-S 839, 17 rue du Fer à Moulin, 75005, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Institut du Fer à Moulin, Paris, France.
Aude
A
Muzerelle
Inserm UMR-S 839, 17 rue du Fer à Moulin, 75005, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Institut du Fer à Moulin, Paris, France.
Sophie
S
Scotto-Lomassese
Université Pierre et Marie Curie, Paris, France.|Inserm UMR- 894, Centre Psychiatrie St Anne, Paris, France.
Jean François
JF
Bernard
Inserm UMR-S 839, 17 rue du Fer à Moulin, 75005, Paris, France.|Université Pierre et Marie Curie, Paris, France.|Institut du Fer à Moulin, Paris, France.
Mariano
M
Soiza-Reilly
Inserm UMR-S 839, 17 rue du Fer à Moulin, 75005, Paris, France. patricia.gaspar@inserm.fr.|Université Pierre et Marie Curie, Paris, France. patricia.gaspar@inserm.fr.|Institut du Fer à Moulin, Paris, France. patricia.gaspar@inserm.fr.
Patricia
P
Gaspar
D020121:5' Untranslated Regions; D000818:Animals; D001933:Brain Stem / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D019426:Integrases / Q000235:genetics; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D066267:Midbrain Raphe Nuclei / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D009434:Neural Pathways / Q000378:metabolism / Q000502:physiology; D056347:Neuroanatomical Tract-Tracing Techniques / Q000379:methods*; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D059326:Serotonergic Neurons / Q000378:metabolism / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
D020121:5' Untranslated Regions; D050486:Serotonin Plasma Membrane Transport Proteins; C493231:Slc6a4 protein, mouse; D012701:Serotonin; C045073:Cre recombinase; D019426:Integrases
AAV; Amygdala; Anatomical tract-tracing; Axon tracing; Dorsal raphe; GFP; Genetic mouse models; Habenula; Hippocampus; Median raphe; Olfactory bulb; Pearson correlation; Prefrontal cortex; SERT; Serotonin; Tegmental nucleus