Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBötzinger complexin vitro
European Journal of Neuroscience. 2008-08-01; 28(3): 510-520
DOI: 10.1111/j.1460-9568.2008.06345.x
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1. Eur J Neurosci. 2008 Aug;28(3):510-20. doi: 10.1111/j.1460-9568.2008.06345.x.
Brain-derived neurotrophic factor enhances fetal respiratory rhythm frequency in
the mouse preBötzinger complex in vitro.
Bouvier J(1), Autran S, Dehorter N, Katz DM, Champagnat J, Fortin G,
Thoby-Brisson M.
Author information:
(1)Laboratoire de Neurobiologie Génétique et Intégrative, Institut Alfred
Fessard, Centre National de la Recherche Scientifique, 91198 Gif sur Yvette,
France.
Brain-derived neurotrophic factor (BDNF) is required during the prenatal period
for normal development of the respiratory central command; however, the
underlying mechanisms remain unknown. To approach this issue, the present study
examined BDNF regulation of fetal respiratory rhythm generation in the
preBötzinger complex (preBötC) of the mouse, using transverse brainstem slices
obtained from prenatal day 16.5 animals. BDNF application (100 ng/mL, 15 min)
increased the frequency of rhythmic population activity in the preBötC by 43%.
This effect was not observed when preparations were exposed to nerve growth
factor (100 ng/mL, 30 min) or pretreated with the tyrosine kinase inhibitor K252a
(1 h, 200 nm), suggesting that BDNF regulation of preBötC activity requires
activation of its cognate tyrosine receptor kinase, TrkB. Consistent with this
finding, single-cell reverse transcription-polymerase chain reaction experiments
showed that one third of the rhythmically active preBötC neurons analysed
expressed TrkB mRNA. Moreover, 20% expressed BDNF mRNA, suggesting that the
preBötC is both a target and a source of BDNF. At the network level, BDNF
augmented activity of preBötC glutamatergic neurons and potentiated glutamatergic
synaptic drives in respiratory neurons by 34%. At the cellular level, BDNF
increased the activity frequency of endogenously bursting neurons by 53.3% but
had no effect on basal membrane properties of respiratory follower neurons,
including the Ih current. Our data indicate that BDNF signalling through TrkB can
acutely modulate fetal respiratory rhythm in association with increased
glutamatergic drive and bursting activity in the preBötC.
DOI: 10.1111/j.1460-9568.2008.06345.x
PMCID: PMC2664708
PMID: 18702723 [Indexed for MEDLINE]