TY - JOUR
T1 - Brain-derived neurotrophic factor selectively regulates dendritogenesis of parvalbumin-containing interneurons in the main olfactory bulb through the PLCgamma pathway
AU - Berghuis, Paul
AU - Agerman, Karin
AU - Dobszay, Marton B
AU - Minichiello, Liliana
AU - Harkany, Tibor
AU - Ernfors, Patrik
N1 - Copyright 2006 Wiley Periodicals, Inc.
PY - 2006
Y1 - 2006
N2 - 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.
AB - 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.
U2 - 10.1002/neu.20319
DO - 10.1002/neu.20319
M3 - Article
C2 - 17013928
SN - 0022-3034
VL - 66
SP - 1437
EP - 1451
JO - Journal of neurobiology
JF - Journal of neurobiology
IS - 13
ER -