Serotonin receptor 2C regulates neurite growth and is necessary for normal retinal processing of visual information.

Autor: Trakhtenberg EF; 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., Pita-Thomas W; 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., Fernandez SG; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida., Patel KH; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida., Venugopalan P; 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., Shechter JM; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida., Morkin MI; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida., Galvao J; Shiley Eye Center, University of California, San Diego, California., Liu X; Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, Florida., Dombrowski SM; Genomatix Software, Ann Arbor, Michigan.; Department of Obstetrics & Gynecology, Wayne State University School of Medicine, Detroit, Michigan., Goldberg JL; 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.
Jazyk: angličtina
Zdroj: Developmental neurobiology [Dev Neurobiol] 2017 Apr; Vol. 77 (4), pp. 419-437. Date of Electronic Publication: 2016 Apr 07.
DOI: 10.1002/dneu.22391
Abstrakt: 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.
(© 2016 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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