Brain-derived neurotrophic factor selectively regulates dendritogenesis of parvalbumin-containing interneurons in the main olfactory bulb through the PLCgamma pathway

J Neurobiol. 2006 Nov;66(13):1437-51. doi: 10.1002/neu.20319.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / deficiency
  • Brain-Derived Neurotrophic Factor / pharmacology*
  • Cells, Cultured
  • Dendrites / drug effects*
  • Dendrites / ultrastructure
  • Drug Interactions
  • Gene Expression Regulation, Developmental / drug effects
  • Gene Expression Regulation, Developmental / physiology
  • Immunohistochemistry / methods
  • Interneurons* / cytology
  • Interneurons* / drug effects
  • Interneurons* / metabolism
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Mice
  • Mice, Transgenic
  • Nerve Tissue Proteins / metabolism
  • Olfactory Bulb / cytology*
  • Parvalbumins / metabolism*
  • Patch-Clamp Techniques / methods
  • Phospholipase C gamma / metabolism*
  • Phospholipase C gamma / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkB / genetics
  • Signal Transduction / physiology
  • Silver Staining / methods


  • Brain-Derived Neurotrophic Factor
  • Nerve Tissue Proteins
  • Parvalbumins
  • Receptor, trkB
  • Phospholipase C gamma