title: Serotonin receptor 2C regulates neurite growth and is necessary for normal retinal processing of visual information.
abstract: Serotonin (5HT) is present in a subpopulation of amacrine cells, which form synapses with retinal ganglion cells (RGCs), but little is known about the physiological role of retinal serotonergic circuitry. We found that the 5HT receptor 2C (5HTR2C) is upregulated in RGCs after birth. Amacrine cells generate 5HT and about half of RGCs respond to 5HTR2C agonism with calcium elevation. We found that there are on average 83 5HT+ amacrine cells randomly distributed across the adult mouse retina, all negative for choline acetyltransferase and 90% positive for tyrosine hydroxylase. We also investigated whether 5HTR2C and 5HTR5A affect RGC neurite growth. We found that both suppress neurite growth, and that RGCs from the 5HTR2C knockout (KO) mice grow longer neurites. Furthermore, 5HTR2C is subject to post-transcriptional editing, and we found that only the edited isoform's suppressive effect on neurite growth could be reversed by a 5HTR2C inverse agonist. Next, we investigated the physiological role of 5HTR2C in the retina, and found that 5HTR2C KO mice showed increased amplitude on pattern electroretinogram. Finally, RGC transcriptional profiling and pathways analysis suggested partial developmental compensation for 5HTR2C absence. Taken together, our findings demonstrate that 5HTR2C regulates neurite growth and RGC activity and is necessary for normal amplitude of RGC response to physiologic stimuli, and raise the hypothesis that these functions are modulated by a subset of 5HT+/ChAT-/TH+ amacrine cells as part of retinal serotonergic circuitry. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital, Department of Neurosurgery, Harvard Medical School, Boston, Massachusetts.|Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.|Neuroscience Program, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Ephraim F
authors.initials: EF
authors.lastname: Trakhtenberg
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.|Department of Anatomy and Neurobiology, Washington University, St. Louis, Missouri.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Pita-Thomas
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Stephanie G
authors.initials: SG
authors.lastname: Fernandez
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Karan H
authors.initials: KH
authors.lastname: Patel
authors.affiliation: F.M. Kirby Neurobiology Center, Boston Children's Hospital, Department of Neurosurgery, Harvard Medical School, Boston, Massachusetts.|Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Praseeda
authors.initials: P
authors.lastname: Venugopalan
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Jesse M
authors.initials: JM
authors.lastname: Shechter
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Melina I
authors.initials: MI
authors.lastname: Morkin
authors.affiliation: Shiley Eye Center, University of California, San Diego, California.
authors.forename: Joana
authors.initials: J
authors.lastname: Galvao
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.
authors.forename: Xiongfei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Genomatix Software, Ann Arbor, Michigan.|Department of Obstetrics & Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
authors.forename: Susan M
authors.initials: SM
authors.lastname: Dombrowski
authors.affiliation: Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida.|Neuroscience Program, University of Miami Miller School of Medicine, Miami, Florida.|Shiley Eye Center, University of California, San Diego, California.|Byers Eye Institute, Stanford University, Palo Alto, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Goldberg
mesh_terms: D025042:Amacrine Cells / Q000502:physiology*; D000818:Animals; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000502:physiology*; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D011985:Receptors, Serotonin; D012165:Retinal Ganglion Cells / Q000502:physiology*; D058826:Serotonin 5-HT2 Receptor Agonists / Q000494:pharmacology*; D014785:Vision, Ocular / Q000502:physiology*
chemical_list: C000599853:5-hydroxytryptamine2C receptor, mouse; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D058826:Serotonin 5-HT2 Receptor Agonists; C078730:serotonin 5 receptor
keywords: 5HTR2C; 5HTR5A; amacrine cell; neurite growth; retinal ganglion cell; serotonin