Projections and interconnections of genetically defined serotonin neurons in mice
Open accessAbstract
Brain serotonin neurons are heterogeneous and can be distinguished by several anatomical and physiological characteristics. Toward resolving this heterogeneity into classes of functional relevance, subtypes of mature serotonin neurons were previously identified based on gene expression differences initiated during development in different rhombomeric (r) segments of the hindbrain. This redefinition of mature serotonin neuron subtypes based on the criteria of genetic lineage, along with the enabling genetic fate mapping tools, now allows various functional properties, such as axonal projections, to be allocated onto these identified subtypes. Furthermore, our approach uniquely enables interconnections between the different serotonin neuron subtypes to be determined; this is especially relevant because serotonin neuron activity is regulated by several feedback mechanisms. We used intersectional and subtractive genetic fate mapping tools to generate three independent lines of mice in which serotonin neurons arising in different rhombomeric segments, either r1, r2 or both r3 and r5, were uniquely distinguished from all other serotonin neurons by their expression of enhanced green fluorescent protein. Each of these subgroups of serotonergic neurons had a unique combination of forebrain projection targets. Typically more than one subgroup innervated an individual target area. Unique patterns of interconnections between the different groups of serotonin neurons were also observed and these pathways could subserve feedback regulatory circuits. Overall, the current findings suggest that activation of subsets of serotonin neurons could result in topographic serotonin release in the forebrain coupled with feedback inhibition of serotonin neurons with alternative projection targets.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Serotonergic projections from the dorsal and medial Raphe nuclei are among the first to emerge and arrive in the PFC around E16/E17 in rodents and postnatal weeks 10-13 in humans.
“The brain matures from the brainstem to the more frontal cortical regions, and it is therefore not surprising that serotonergic projections from both the dorsal as well as the medial Raphe nuclei (DRN, MRN respectively) are among the first to emerge and are set towards cortical regions where they arrive in the PFC around E16/E17 in rodent and week postnatal 10–13 in humans [113–116].”
From Development of prefrontal cortex (2022) · cites this paper as [116]
The Results (‘Major efferent projections’; page unavailable) report cortical innervation by r1-Pet1 neurons, predominantly originating in the dorsal raphe, and medial prefrontal innervation by r2-Pet1 neurons. The paper studies projections in mice but does not establish that these projections are among the first to emerge or give the claimed E16/E17 rodent and postnatal-week-10–13 human arrival times. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
A review of central 5-HT receptors and their function
Barnes, N. M., & Sharp, T. (1999) · Neuropharmacology · doi:10.1016/s0028-3908(99)00010-6 · Cited by 3,150 · see citing works
Handbook of chemical neuroanatomy
(2005) · Handbook of chemical neuroanatomy · doi:10.1016/s0924-8196(05)80001-6 · Cited by 906 · see citing works
Hisano, S., Hoshi, K., Ikeda, Y., Maruyama, D., Kanemoto, M., Ichijo, H., Kojima, I., Takeda, J., & Nogami, H. (2000) · Molecular Brain Research · doi:10.1016/s0169-328x(00)00194-7 · Cited by 806 · see citing works
Anatomy of the Serotonergic Systema
Törk, I. (1990) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1990.tb16870.x · Cited by 557 · see citing works
O’Hearn, E., Battaglia, G., Souza, E. B. D., Kuhar, M. J., & Me, M. (1988) · Journal of Neuroscience · doi:10.1523/jneurosci.08-08-02788.1988 · Cited by 543 · see citing works
Hendricks, T. J., Fyodorov, D., Wegman, L. J., Lelutiu, N. B., Pehek, E. A., Yamamoto, B., Silver, J., Weeber, E., Sweatt, J., & Deneris, E. S. (2003) · Neuron · doi:10.1016/s0896-6273(02)01167-4 · Cited by 486 · see citing works
Skagerberg, G., & Björklund, A. (1985) · Neuroscience · doi:10.1016/0306-4522(85)90225-8 · Cited by 415 · see citing works
Kosofsky, B. E., & Molliver, M. E. (1987) · Synapse · doi:10.1002/syn.890010204 · Cited by 412 · see citing works
Two lineage boundaries coordinate vertebrate apical ectodermal ridge formationPreprint
Kimmel, R. A., Turnbull, D. H., Blanquet, V., Wurst, W., Loomis, C. A., & Joyner, A. L. (2000) · Genes & Development · doi:10.1101/gad.14.11.1377 · Cited by 341 · see citing works
Hendricks, T. J., Francis, N. J., Fyodorov, D. V., & Deneris, E. S. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-23-10348.1999 · Cited by 300 · see citing works
Reward and the serotonergic system
Kranz, G. S., Kasper, S. F., & Lanzenberger, R. R. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.01.036 · Cited by 270 · see citing works
Redefining the serotonergic system by genetic lineage
Jensen, P., Farago, A. F., Awatramani, R. B., Scott, M. M., Deneris, E. S., & Dymecki, S. M. (2008) · Nature Neuroscience · doi:10.1038/nn2050 · Cited by 244 · see citing works
Hale, M. W., & Lowry, C. A. (2010) · Psychopharmacology · doi:10.1007/s00213-010-2089-z · Cited by 243 · see citing works
Mamounas, L. A., Mullen, C. A., O’Hearn, E., & Molliver, M. E. (1991) · The Journal of Comparative Neurology · doi:10.1002/cne.903140312 · Cited by 238 · see citing works
Cryptic boundaries in roof plate and choroid plexus identified by intersectional gene activation
Awatramani, R., Soriano, P., Rodriguez, C., Mai, J. J., & Dymecki, S. M. (2003) · Nature Genetics · doi:10.1038/ng1228 · Cited by 215 · see citing works
Self-citationBeitz, A. J. (1982) · Journal of Neuroscience · doi:10.1523/jneurosci.02-07-00829.1982 · Cited by 202 · see citing works
Bland, S. T., Hargrave, D., Pepin, J. L., Amat, J., Watkins, L. R., & Maier, S. F. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300206 · Cited by 155 · see citing works
Wilson, M. A., & Molliver, M. E. (1991) · Neuroscience · doi:10.1016/0306-4522(91)90076-z · Cited by 152 · see citing works
Waselus, M., Valentino, R. J., & Van Bockstaele, E. J. (2011) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2011.05.011 · Cited by 142 · see citing works
Kirby, L. G., & Lucki, I. (1997) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)36846-6 · Cited by 141 · see citing works
Kiyasova, V., Fernández, S. P., Lainé, J., Stankovski, L., Muzerelle, A., Doly, S., & Gaspar, P. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.4080-10.2011 · Cited by 138 · see citing works
Linking Genetically Defined Neurons to Behavior through a Broadly Applicable Silencing Allele
Kim, J. C., Cook, M. N., Carey, M. R., Shen, C., Regehr, W. G., & Dymecki, S. M. (2009) · Neuron · doi:10.1016/j.neuron.2009.07.010 · Cited by 134 · see citing works
Self-citationSmith, Y., Kieval, J. Z., Couceyro, P. R., & Kuhar, M. J. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990517)407:4 · Cited by 122 · see citing works
Dorsal raphe nuclear stimulation of SCN serotonin release and circadian phase-resetting
Glass, J. D., DiNardo, L. A., & Ehlen, J. C. (2000) · Brain Research · doi:10.1016/s0006-8993(00)01963-6 · Cited by 106 · see citing works
Mapping cell fate and function using recombinase-based intersectional strategies
Dymecki, S. M., Ray, R. S., & Kim, J. C. (2010) · Methods in Enzymology · doi:10.1016/s0076-6879(10)77011-7 · Cited by 104 · see citing works
Self-citationSinger, S., Rossi, S., Verzosa, S., Hashim, A. T., Lonow, R., Cooper, T. B., Sershen, H. W., & Lajtha, Á. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000035814.45494.15 · Cited by 98 · see citing works
Hindbrain patterning:Krox20couples segmentation and specification of regional identity
Voiculescu, O., Taillebourg, E., Pujades, C., et al. (2001) · Development · doi:10.1242/dev.128.24.4967 · Cited by 97 · see citing works
Meyer-Bernstein, E. L., & Morin, L. P. (1999) · Neuroscience · doi:10.1016/s0306-4522(98)00733-7 · Cited by 96 · see citing works
Hornung, J., & Celio, M. R. (1992) · The Journal of Comparative Neurology · doi:10.1002/cne.903200404 · Cited by 94 · see citing works
Is there a direct retina-raphe-suprachiasmatic nucleus pathway in the rat?
Kawano, H., Decker, K., & Reuss, S. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12795-6 · Cited by 88 · see citing works
Waterhouse, B. D., Moises, H. C., & Woodward, D. J. (1986) · Brain Research Bulletin · doi:10.1016/0361-9230(86)90218-2 · Cited by 83 · see citing works
Vasudeva, R. K., Lin, R. C. S., Simpson, K. L., & Waterhouse, B. D. (2011) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2011.05.008 · Cited by 78 · see citing works
Li, Y., Li, H., Kaneko, T., & Mizuno, N. (2001) · Brain Research · doi:10.1016/s0006-8993(01)02272-7 · Cited by 71 · see citing works
Commons, K. G. (2008) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2008.06235.x · Cited by 42 · see citing works
Self-citationPhenotype and function of raphe projections to the suprachiasmatic nucleus
Yamakawa, G. R., & Antle, M. C. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07228.x · Cited by 39 · see citing works
Sperling, R. E., & Commons, K. G. (2011) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2011.07677.x · Cited by 31 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 2
- Paxinos G Franklin KBJ The Mouse Brain in Stereotaxic Coordinates 2001 Deluxe edition of the atlas second edition San Diego, CA Academic Press
- Swanson LW Brain maps: structure of the rat brain An atlas with printed and electronic templates for data, models, and schematics 2004 3rd edition Amsterdam Elsevier Academic Press
Cited by
Sorted by citations
Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378 · see citing works
Albert, P. R., Vahid-Ansari, F., & Luckhart, C. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00199 · Cited by 321 · see citing works
Embracing diversity in the 5-HT neuronal system
Okaty, B. W., Commons, K. G., & Dymecki, S. M. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0151-3 · Cited by 319 · see citing works
Self-citationRen, J., Isakova, A., Friedmann, D., Zeng, J., Grutzner, S. M., Pun, A., Zhao, G. Q., Kolluru, S. S., Wang, R., Lin, R., et al. (2019) · eLife · doi:10.7554/elife.49424 · Cited by 304 · see citing works
Muzerelle, A., Scotto-Lomassese, S., Bernard, J. F., Soiza-Reilly, M., & Gaspar, P. (2016) · Brain Structure and Function · doi:10.1007/s00429-014-0924-4 · Cited by 303 · see citing works
Molecular and anatomical organization of the dorsal raphe nucleus
Huang, K. W., Ochandarena, N. E., Philson, A. C., Hyun, M., Birnbaum, J. E., Cicconet, M., & Sabatini, B. L. (2019) · eLife · doi:10.7554/elife.46464 · Cited by 267 · see citing works
Multi-Scale molecular deconstruction of the serotonin neuron system
Okaty, B. W., Freret, M. E., Rood, B. D., Brust, R. D., Hennessy, M. L., deBairos, D., Kim, J. C., Cook, M. N., & Dymecki, S. M. (2015) · Neuron · doi:10.1016/j.neuron.2015.10.007 · Cited by 217 · see citing works
Self-citationActivity of Raphé serotonergic neurons controls emotional behaviors
Teissier, A., Chemiakine, A., Inbar, B., Bagchi, S., Ray, R. S., Palmiter, R. D., Dymecki, S. M., Moore, H., & Ansorge, M. S. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.10.061 · Cited by 197 · see citing works
Self-citationRaphe GABAergic Neurons Mediate the Acquisition of Avoidance after Social Defeat
Challis, C., Boulden, J., Veerakumar, A., Espallergues, J., Vassoler, F. M., Pierce, R. C., Beck, S. G., & Berton, O. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2383-13.2013 · Cited by 197 · see citing works
Comparative density of CCK- and PV-GABA cells within the cortex and hippocampus
Whissell, P. D., Cajanding, J. D., Fogel, N., & Kim, J. C. (2015) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2015.00124 · Cited by 118 · see citing works
Identification of serotonergic neuronal modules that affect aggressive behavior
Niederkofler, V., Asher, T. E., Okaty, B. W., Rood, B. D., Narayan, A., Hwa, L. S., Beck, S. G., Miczek, K. A., & Dymecki, S. M. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.10.063 · Cited by 113 · see citing works
Alonso, A., Merchán, P., Sandoval, J. E., Sánchez-Arrones, L., Garcia-Cazorla, A., Artuch, R., Ferrán, J. L., Martínez-de-la-Torre, M., & Puelles, L. (2013) · Brain Structure and Function · doi:10.1007/s00429-012-0456-8 · Cited by 113 · see citing works
Fernandez, S. P., Cauli, B., Cabezas, C., Muzerelle, A., Poncer, J.-C., & Gaspar, P. (2016) · Brain Structure and Function · doi:10.1007/s00429-015-1142-4 · Cited by 100 · see citing works
Neocortical layer 5 subclasses: from cellular properties to roles in behavior
Moberg, S., & Takahashi, N. (2022) · Frontiers in Synaptic Neuroscience · doi:10.3389/fnsyn.2022.1006773 · Cited by 62 · see citing works
Essentials of Recombinase-Based Genetic Fate Mapping in Mice
Jensen, P., & Dymecki, S. M. (2014) · Methods in Molecular Biology · doi:10.1007/978-1-60327-292-6_26 · Cited by 54 · see citing works
Self-citationSargin, D., Jeoung, H.-S., Goodfellow, N. M., & Lambe, E. K. (2019) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.9b00073 · Cited by 54 · see citing works
Witteveen, J. S., Middelman, A., van Hulten, J. A., Martens, G. J. M., Homberg, J. R., & Kolk, S. M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00143 · Cited by 53 · see citing works
Garcia, L. P., Witteveen, J. S., Middelman, A., van Hulten, J. A., Martens, G. J. M., Homberg, J. R., & Kolk, S. M. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1105-x · Cited by 28 · see citing works
- Authors
- Bang, S. J., Jensen, P., Dymecki, S. M., & Commons, K. G.
- Affiliations
- Boston Children's Hospital (US)
- National Institutes of Health (US)
- Harvard University (US)
- Corresponding author
- Commons, Kathryn G.
- Venue
- European Journal of Neuroscience
- Publisher
- Wiley
- Published
- 2011-12-13
- Volume
- 35
- Issue
- 1
- Pages
- 85-96
- ISSN
- 0953-816X (ISSN-L)
- 1460-9568
- PMC
- PMC3268345
- OpenAlex
- W1929691281
- Cited by
- 181
- References
- 36
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 9 · 2023: 10 · 2022: 15 · 2021: 12 · 2020: 19 · 2019: 17 · 2018: 15 · 2017: 12 · 2016: 7 · 2015: 20 · 2014: 14 · 2013: 12 · 2012: 8
- FWCI
- 4.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute on Drug Abuse (R21DA023643, R01DA021801)
- National Institute of Environmental Health Sciences
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P01HD036379)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- serotonergic neurons, hindbrain development, genetic fate mapping, axonal projections, forebrain projections, product inhibition
- MeSH terms
- Animals, Brain, Mice, Transgenic, Neural Pathways, Gene Expression Regulation, Developmental, Green Fluorescent Proteins, Mice, Serotonergic Neurons
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
