Brain-derived neurotrophic factor signaling in the HVC is required for testosterone-induced song of female canaries.
Testosterone-induced singing in songbirds is thought to involve testosterone-dependent morphological changes that include angiogenesis and neuronal recruitment into the HVC, a central part of the song control circuit. Previous work showed that testosterone induces the production of vascular endothelial growth factor (VEGF) and its receptor (VEGFR2 tyrosine kinase), which in turn leads to an upregulation of brain-derived neurotrophic factor (BDNF) production in HVC endothelial cells. Here we report for the first time that systemic inhibition of the VEGFR2 tyrosine kinase is sufficient to block testosterone-induced song in adult female canaries, despite sustained androgen exposure and the persistence of the effects of testosterone on HVC morphology. Expression of exogenous BDNF in HVC, induced locally by in situ transfection, reversed the VEGFR2 inhibition-mediated blockade of song development, thereby restoring the behavioral phenotype associated with androgen-induced song. The VEGFR2-inhibited, BDNF-treated females developed elaborate male-like song that included large syllable repertoires and high syllable repetition rates, features known to attract females. Importantly, although functionally competent new neurons were recruited to HVC after testosterone treatment, the time course of neuronal addition appeared to follow BDNF-induced song development. These findings indicate that testosterone-associated VEGFR2 activity is required for androgen-induced song in adult songbirds and that the behavioral effects of VEGFR2 inhibition can be rescued by BDNF within the adult HVC.
Hartog
Tessa E
TE
Institute for Neuroscience, VU University Amsterdam, 1081 HV Amsterdam, The Netherlands.
Dittrich
Falk
F
Pieneman
Anton W
AW
Jansen
René F
RF
Frankl-Vilches
Carolina
C
Lessmann
Volkmar
V
Lilliehook
Christina
C
Goldman
Steven A
SA
Gahr
Manfred
M
D000818:Animals; D001921:Brain / Q000033:anatomy & histology / Q000166:cytology / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002171:Canaries; D002452:Cell Count; D005260:Female; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009929:Organ Size; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011897:Random Allocation; D013018:Sound Spectrography; D013739:Testosterone / Q000378:metabolism*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000378:metabolism; D014828:Vocalization, Animal / Q000502:physiology*
D019208:Brain-Derived Neurotrophic Factor; D013739:Testosterone; D011505:Protein-Tyrosine Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2