title: Brain-derived neurotrophic factor-induced potentiation of Ca(2+) oscillations in developing cortical neurons.
abstract: Brain-derived neurotrophic factor (BDNF) has been reported to exert an acute potentiation of synaptic activity. Here we examined the action of BDNF on synchronous spontaneous Ca(2+) oscillations in cultured cerebral cortical neurons prepared from postnatal 2-3-day-old rats. The synchronous spontaneous Ca(2+) oscillations began at approximately DIV 5. It was revealed that voltage-dependent Ca(2+) channels and ionotropic glutamate receptors were involved in the synchronous spontaneous oscillatory activity. BDNF potentiated the frequency of these oscillations. The BDNF-potentiated activity reached 207 +/- 20.1% of basal oscillatory activity. NT-3 and NT-4/5 also induced the potentiation. However, nerve growth factor did not. We examined the correlation between BDNF-induced glutamate release and the BDNF-potentiated oscillatory activity. Both up-regulation of phospholipase C-gamma (PLC-gamma) expression and the BDNF-induced glutamate release occurred at approximately DIV 5 when the BDNF-potentiated oscillations appeared. We confirmed that the BDNF-induced glutamate release occurred through a glutamate transporter that was dependent on the PLC-gamma/IP(3)/Ca(2+) pathway. Transporter inhibitors blocked the BDNF-potentiated oscillations, demonstrating that BDNF enhanced the glutamatergic transmissions in the developing cortical network by inducing glutamate release via a glutamate transporter.
authors.affiliation: Division of Protein Biosynthesis, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan. numakawa@protein.osaka-u.ac.jp
authors.forename: Tadahiro
authors.initials: T
authors.lastname: Numakawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Adachi
authors.forename: Tomoya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Daisaku
authors.initials: D
authors.lastname: Yokomaku
authors.forename: Masashi
authors.initials: M
authors.lastname: Yamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hatanaka
mesh_terms: D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D015513:Oncogene Proteins / Q000378:metabolism; D009991:Oscillometry; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051966:Phospholipase C gamma; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D019208:Brain-Derived Neurotrophic Factor; D007527:Isoenzymes; D018377:Neurotransmitter Agents; D015513:Oncogene Proteins; C065400:oncogene protein trk; D018698:Glutamic Acid; D019869:Phosphatidylinositol 3-Kinases; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma