title: Axonal control of the adult neural stem cell niche.
abstract: The ventricular-subventricular zone (V-SVZ) is an extensive germinal niche containing neural stem cells (NSCs) in the walls of the lateral ventricles of the adult brain. How the adult brain's neural activity influences the behavior of adult NSCs remains largely unknown. We show that serotonergic (5HT) axons originating from a small group of neurons in the raphe form an extensive plexus on most of the ventricular walls. Electron microscopy revealed intimate contacts between 5HT axons and NSCs (B1) or ependymal cells (E1) and these cells were labeled by a transsynaptic viral tracer injected into the raphe. B1 cells express the 5HT receptors 2C and 5A. Electrophysiology showed that activation of these receptors in B1 cells induced small inward currents. Intraventricular infusion of 5HT2C agonist or antagonist increased or decreased V-SVZ proliferation, respectively. These results indicate that supraependymal 5HT axons directly interact with NSCs to regulate neurogenesis via 5HT2C.
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Cheuk Ka
authors.initials: CK
authors.lastname: Tong
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Jiadong
authors.initials: J
authors.lastname: Chen
authors.affiliation: Laboratory of Comparative Neurobiology, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia 46980, Spain.
authors.forename: Arantxa
authors.initials: A
authors.lastname: Cebrián-Silla
authors.affiliation: Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ 85013, USA.
authors.forename: Zaman
authors.initials: Z
authors.lastname: Mirzadeh
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Obernier
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Cristina D
authors.initials: CD
authors.lastname: Guinto
authors.affiliation: Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Laurence H
authors.initials: LH
authors.lastname: Tecott
authors.affiliation: Laboratory of Comparative Neurobiology, Instituto Cavanilles, Universidad de Valencia, CIBERNED, Valencia 46980, Spain; Unidad Mixta de Esclerosis Múltiple y Neurorregeneración, IIS Hospital La Fe, Valencia 46013, Spain.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: García-Verdugo
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Kriegstein
authors.affiliation: Department of Neurological Surgery and The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, San Francisco, CA 94143, USA; Neuroscience Graduate Program, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: abuylla@stemcell.ucsf.edu.
authors.forename: Arturo
authors.initials: A
authors.lastname: Alvarez-Buylla
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000166:cytology / Q000502:physiology; D002454:Cell Differentiation; D049109:Cell Proliferation; D004594:Electrophysiology; D007124:Immunoenzyme Techniques; D051379:Mice; D008854:Microscopy, Electron; D058953:Neural Stem Cells / Q000166:cytology* / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology*; D060888:Real-Time Polymerase Chain Reaction; D044405:Receptor, Serotonin, 5-HT2C / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D055153:Stem Cell Niche
chemical_list: D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D017366:Serotonin Receptor Agonists