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Ascending serotonin neuron diversity under two umbrellas

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Abstract

Forebrain serotonin relevant for many psychological disorders arises in the hindbrain, primarily within the dorsal and median raphe nuclei (DR and MR). These nuclei are heterogeneous, containing several distinct groups of serotonin neurons. Here, new insight into the afferent and efferent connectivity of these areas is reviewed in correlation with their developmental origin. These data suggest that the caudal third of the DR, the area originally designated B6, may be misidentified as part of the DR as it shares many features of connectivity with the MR. By considering the rostral DR independently and affiliating the B6 to the MR, the diverse subgroups of serotonin neurons can be arranged with more coherence into two umbrella groups, each with distinctive domains of influence. Serotonin neurons within the rostral DR are uniquely interconnected with brain areas associated with emotion and motivation such as the amygdala, accumbens and ventral pallidum. In contrast serotonin neurons in the B6 and MR are characterized by their dominion over the septum and hippocampus. This distinction between the DR and B6/MR parallels their developmental origin and likely impacts their role in both behavior and psychopathology. Implications and further subdivisions within these areas are discussed.

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Acknowledgments

Thanks to Dr. Patricia Gaspar for generous permission to use a modified figure from Muzerelle et al. as well as for comments on the manuscript. Additional thoughtful comments were provided by Drs. Daniel Ehlinger, Jessica Babb (Boston Children’s Hospital/Harvard Medical School), Dr. Bernat Kocsis (Beth Israel Deaconess/Harvard Medical School), Dr. Ben Okaty, Dr. Susan Dymecki (Harvard Medical School) and the reviewers; although all omissions, over-simplifications and errors remain my own. Funding provided by the National Institutes of Health Grants DA021801 and HD036379, the Brain and Behavior Foundation NARSAD Independent Investigator Award, and the Sara Page Mayo Foundation for Pediatric Pain Research.

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  1. Department of Anesthesiology, Perioperative, and Pain Medicine, Boston Children’s Hospital, 300 Longwood Ave., Boston, MA, 02115, USA

    Kathryn G. Commons

  2. Department of Anaesthesia, Harvard Medical School, Boston, USA

    Kathryn G. Commons

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Commons, K.G. Ascending serotonin neuron diversity under two umbrellas. Brain Struct Funct 221, 3347–3360 (2016). https://doi.org/10.1007/s00429-015-1176-7

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