title: Brain-derived neurotrophic factor selectively regulates dendritogenesis of parvalbumin-containing interneurons in the main olfactory bulb through the PLCgamma pathway.
abstract: Molecular mechanisms of neurotrophin signaling on dendrite development and dynamics are only partly understood. To address the role of brain-derived neurotrophic factor (BDNF) in the morphogenesis of GABAergic neurons of the main olfactory bulb, we analyzed mice lacking BDNF, mice carrying neurotrophin-3 (NT3) in the place of BDNF, and TrkB signaling mutant mice with a receptor that can activate phospholipase Cgamma (PLCgamma) but is unable to recruit the adaptors Shc/Frs2. BDNF deletion yielded a compressed olfactory bulb with a significant loss of parvalbumin (PV) immunoreactivity in GABAergic interneurons of the external plexiform layer. Dendrite development of PV-positive interneurons was selectively attenuated by BDNF since other Ca2+ -binding protein-containing neuron populations appeared unaffected. The deficit in PV-positive neurons could be rescued by the NT3/NT3 alleles. The degree of PV immunoreactivity was dependent on BDNF and TrkB recruitment of the adaptor proteins Shc/Frs2. In contrast, PLCgamma signaling from the TrkB receptor was sufficient for dendrite growth in vivo and consistently, blocking PLCgamma prevented BDNF-dependent dendrite development in vitro. Collectively, our results provide genetic evidence that BDNF and TrkB signaling selectively regulate PV expression and dendrite growth in a subset of neurochemically-defined GABAergic interneurons via activation of the PLCgamma pathway.
authors.affiliation: Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden. Patrik.Ernfors@ki.se
authors.forename: Paul
authors.initials: P
authors.lastname: Berghuis
authors.forename: Karin
authors.initials: K
authors.lastname: Agerman
authors.forename: Marton B
authors.initials: MB
authors.lastname: Dobszay
authors.forename: Liliana
authors.initials: L
authors.lastname: Minichiello
authors.forename: Tibor
authors.initials: T
authors.lastname: Harkany
authors.forename: Patrik
authors.initials: P
authors.lastname: Ernfors
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000172:deficiency / Q000494:pharmacology*; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects* / Q000648:ultrastructure; D004347:Drug Interactions; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D007150:Immunohistochemistry / Q000379:methods; D007395:Interneurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology*; D010320:Parvalbumins / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D051966:Phospholipase C gamma / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020813:Receptor, trkB / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D016622:Silver Staining / Q000379:methods
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D020813:Receptor, trkB; D051966:Phospholipase C gamma