title: Connective tissue growth factor regulates interneuron survival and information processing in the olfactory bulb.
abstract: Neurogenesis underlies plastic changes in defined neuronal circuits in the postnatal and adult brain. Here we identify connective tissue growth factor (CTGF) as a critical factor in the mouse olfactory bulb (OB) in determining the efficiency of incorporation of postnatally born inhibitory neurons, thus gating the output of glomeruli, the first relay station of olfactory processing in the brain. In the OB, CTGF expression was restricted to prenatally born external tufted cells. CTGF enhanced the proapoptotic activity of glial-derived TGF-β2, decreasing the survival of periglomerular inhibitory neurons. Changes in CTGF expression levels in the OB led to modifications in local neuronal circuitry and olfactory behaviors. We show that the odorant-specific recruitment of distinct glomeruli resulted in enhanced local CTGF expression levels in the activated glomeruli. Collectively our data reveal a molecular mechanism controlling the survival of defined postnatally born neurons, thus adapting neuronal integration to the sensory experiences.
authors.affiliation: Department of Clinical Neurobiology, Heidelberg University Medical Center, 69120 Heidelberg, Germany; Department of Clinical Neurobiology/A230, German Center for Cancer Research (DKFZ), 69120 Heidelberg, Germany.
authors.forename: Konstantin
authors.initials: K
authors.lastname: Khodosevich
authors.forename: Françoise
authors.initials: F
authors.lastname: Lazarini
authors.forename: Jakob
authors.initials: J
authors.lastname: von Engelhardt
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneko
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Lledo
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001973:Bromodeoxyuridine / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics / Q000378:metabolism*; D004192:Discrimination, Psychological / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D007395:Interneurons / Q000502:physiology*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008297:Male; D057567:Memory, Long-Term / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology* / Q000502:physiology; D009924:Organ Culture Techniques; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018035:Receptors, Odorant / Q000235:genetics / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012684:Sensory Thresholds / Q000502:physiology; D012903:Smell / Q000235:genetics*; D055366:Synaptic Potentials / Q000235:genetics; D014162:Transfection; D016875:tau Proteins / Q000235:genetics
chemical_list: D008164:Luminescent Proteins; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C118713:Olfr16 protein, mouse; D034741:RNA, Small Interfering; D018035:Receptors, Odorant; D018125:Receptors, Transforming Growth Factor beta; D016875:tau Proteins; D055513:Connective Tissue Growth Factor; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D001973:Bromodeoxyuridine; C013411:biocytin; D008239:Lysine