Brain‐derived neurotrophic factor enhances fetal respiratory rhythm frequency in the mouse preBötzinger complex in vitro
- 23 July 2008
- journal article
- Published by Wiley in European Journal of Neuroscience
- Vol. 28 (3), 510-520
- https://doi.org/10.1111/j.1460-9568.2008.06345.x
Abstract
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.Keywords
This publication has 61 references indexed in Scilit:
- Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett SyndromeJournal of Neurophysiology, 2008
- Is the Early Development of Girls with Rett Disorder Really Normal?Pediatric Research, 2005
- Sorting and Activity-Dependent Secretion of BDNF Require Interaction of a Specific Motif with the Sorting Receptor Carboxypeptidase ENeuron, 2005
- Identification of Two Types of Inspiratory Pacemaker Neurons in the Isolated Respiratory Neural Network of MiceJournal of Neurophysiology, 2001
- Characterisation of breathing and associated central autonomic dysfunction in the Rett disorderArchives of Disease in Childhood, 2001
- Trk receptors: mediators of neurotrophin actionCurrent Opinion in Neurobiology, 2001
- Activity-Dependent Release of Endogenous Brain-Derived Neurotrophic Factor from Primary Sensory Neurons Detected by ELISAIn SituJournal of Neuroscience, 2000
- Methyl-CpG-binding protein 2 mutations in Rett syndromeCurrent Opinion in Genetics & Development, 2000
- The Role of the Hyperpolarization-Activated Current in Modulating Rhythmic Activity in the Isolated Respiratory Network of MiceJournal of Neuroscience, 2000
- Neurotrophin-evoked rapid excitation through TrkB receptorsNature, 1999