 |
|||||
|
|||||
|
|||||
|
|||||
|
|||||
The Journal of Neuroscience, January 31, 2007, 27(5):1097-1105; doi:10.1523/JNEUROSCI.3590-06.2007
Previous Article | Next Article
Development/Plasticity/Repair
Endogenous Brain-Derived Neurotrophic Factor Triggers Fast Calcium Transients at Synapses in Developing Dendrites
Susanne B. Lang, Valentin Stein, Tobias Bonhoeffer, andChristian Lohmann Max Planck Institute of Neurobiology, 82152 Martinsried-München, Germany
Correspondence should be addressed to Christian Lohmann, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried-München, Germany. Email: lohmann{at}neuro.mpg.de
Brain-derived neurotrophic factor (BDNF) is involved in many aspects of the formation of functional neuronal networks. BDNF signaling regulates neuronal development not only globally, at the level of entire neurons or networks, but also at a subcellular level and with high temporal specificity; however, the spatiotemporal characteristics of intrinsic BDNF signaling are essentially unknown. Here, we used calcium imaging to directly observe intrinsic BDNF signaling in developing hippocampal neurons. We found that blocking intrinsic BDNF signaling with function-blocking BDNF antibodies (
BDNF) or K252-a reduced the frequency of spontaneously occurring fast and localized calcium rises in dendrites. Conversely, focal application of BDNF evoked fast and local dendritic calcium transients, which required activation of TrkB (tropomyosin-related kinase B) receptors as well as activation of voltage-gated sodium and calcium channels. Virus-mediated expression of PSD-95:CFP (postsynaptic density-95 tagged with cyan fluorescent protein) revealed that spontaneous local calcium transients occurred frequently at postsynaptic sites along the dendrite. The frequency of synaptically localized calcium transients was specifically reduced by blocking intrinsic BDNF signaling, whereas nonsynaptic calcium rises were not affected. Furthermore, focal BDNF delivery evoked localized and fast calcium elevations specifically at postsynaptic sites. Together, our results demonstrate that BDNF-dependent calcium signaling in developing hippocampal neurons is fast and occurs at synapses. These temporal and spatial characteristics of intrinsic BDNF signaling as well as its relative abundance renders BDNF an ideal signaling molecule in the establishment of specific synaptic connectivity and functional neuronal networks.
Key words: calcium signaling; development; BDNF; TrkB; postsynaptic site; hippocampus
Received Aug. 18, 2006; revised Dec. 8, 2006; accepted Dec. 19, 2006.
Correspondence should be addressed to Christian Lohmann, Max Planck Institute of Neurobiology, Am Klopferspitz 18, 82152 Martinsried-München, Germany. Email: lohmann{at}neuro.mpg.de
This article has been cited by other articles:
N. Matsuda, H. Lu, Y. Fukata, J. Noritake, H. Gao, S. Mukherjee, T. Nemoto, M. Fukata, and M.-m. Poo
Differential Activity-Dependent Secretion of Brain-Derived Neurotrophic Factor from Axon and Dendrite
J. Neurosci., November 11, 2009; 29(45): 14185 - 14198.
[Abstract] [Full Text] [PDF]
S. L. Mironov, E. Skorova, N. Hartelt, L. A. Mironova, M. T. Hasan, and S. Kügler
Remodelling of the respiratory network in a mouse model of Rett syndrome depends on brain-derived neurotrophic factor regulated slow calcium buffering
J. Physiol., June 1, 2009; 587(11): 2473 - 2485.
[Abstract] [Full Text] [PDF]
M. D. Amaral and L. Pozzo-Miller
BDNF Induces Calcium Elevations Associated With IBDNF, a Nonselective Cationic Current Mediated by TRPC Channels
J Neurophysiol, October 1, 2007; 98(4): 2476 - 2482.
[Abstract] [Full Text] [PDF]
M. H. Mohajerani, S. Sivakumaran, P. Zacchi, P. Aguilera, and E. Cherubini
Correlated network activity enhances synaptic efficacy via BDNF and the ERK pathway at immature CA3 CA1 connections in the hippocampus
PNAS, August 7, 2007; 104(32): 13176 - 13181.
[Abstract] [Full Text] [PDF]
|
|
|
|
 |
|