Brain-derived neurotrophic factor selectively regulates dendritogenesis of parvalbumin-containing interneurons in the main olfactory bulb through the PLCgamma pathway.
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.
Berghuis
Paul
P
Division of Molecular Neurobiology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S-171 77 Stockholm, Sweden. Patrik.Ernfors@ki.se
Agerman
Karin
K
Dobszay
Marton B
MB
Minichiello
Liliana
L
Harkany
Tibor
T
Ernfors
Patrik
P
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
D019208:Brain-Derived Neurotrophic Factor; D009419:Nerve Tissue Proteins; D010320:Parvalbumins; D020813:Receptor, trkB; D051966:Phospholipase C gamma