| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Received December 16, 2002
Accepted after revision February 18, 2003
1 Center for Aging and Developmental Biology, Department of Pharmacology and Physiology , University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
2 Center for Aging and Developmental Biology, Departments of Pharmacology and Physiology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA
* To whom correspondence should be addressed. E-mail: hermes-yeh{at}urmc.rochester.edu.
In addition to exerting long-term neurotrophic influences on developmental process such as neuronal survival and neuritic outgrowth, brain-derived neurotrophic factor (BDNF) has been reported to modulate synaptic transmission in the short-term. Considerable evidence indicates that BDNF acutely modulates NMDA receptor-mediated synaptic activity. However, whether BDNF modulates inhibitory synaptic transmission remains to be firmly established. In the present study, we examined the effect of acute BDNF exposure on GABA-evoked whole-cell responses as well as GABAergic synaptic activity in cultured mouse cerebellar granule cells. GABA-evoked responses were reduced by 39.5 ± 4.7 % upon acute and focal application of BDNF (100 ng ml-1). The reduction of the GABA response recovered only partially even minutes after removal of BDNF. TrkB-IgG and K252a, but not K252b, prevented the BDNF-induced attenuation of the GABA response. BDNF exposure shifted the cumulative peak amplitude distribution leftward for both spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) without affecting the rise time and decay time constants. Acute exposure to BDNF also resulted in internalization of GABAA receptors in cultured cerebellar granule cells, as reflected by diminished immunostaining with an antibody against the GABAA receptor 
2/3 subunit. Although the BDNF-induced GABAA receptor internalization was sensitive to K252a, it did not become manifest until 5 min after exposure to BDNF. Therefore, receptor internalization alone cannot account for the prompt BDNF-induced attenuation of GABA-mediated activity. We conclude that BDNF modulates GABAA receptor-mediated activity through TrkB receptor signalling that triggers a kinase-dependent short latency effect and a delayed longer latency effect hallmarked by receptor internalization.
This article has been cited by other articles:
|
|
 |
|
  I. Abidin, U. T. Eysel, V. Lessmann, and T. Mittmann Impaired GABAergic inhibition in the visual cortex of brain-derived neurotrophic factor heterozygous knockout mice J. Physiol., April 1, 2008; 586(7): 1885 - 1901. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kron, M. Morschel, J. Reuter, W. Zhang, and M. Dutschmann Developmental changes in brain-derived neurotrophic factor-mediated modulations of synaptic activities in the pontine Kolliker Fuse nucleus of the rat J. Physiol., August 15, 2007; 583(1): 315 - 327. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kanematsu, A. Yasunaga, Y. Mizoguchi, A. Kuratani, J. T. Kittler, J. N. Jovanovic, K. Takenaka, K. I. Nakayama, K. Fukami, T. Takenawa, et al. Modulation of GABAA Receptor Phosphorylation and Membrane Trafficking by Phospholipase C-related Inactive Protein/Protein Phosphatase 1 and 2A Signaling Complex Underlying Brain-derived Neurotrophic Factor-dependent Regulation of GABAergic Inhibition J. Biol. Chem., August 4, 2006; 281(31): 22180 - 22189. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Hewitt and J. S. Bains Brain-Derived Neurotrophic Factor Silences GABA Synapses Onto Hypothalamic Neuroendocrine Cells Through a Postsynaptic Dynamin-Mediated Mechanism J Neurophysiol, April 1, 2006; 95(4): 2193 - 2198. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. H. Woo and B. Lu Regulation of cortical interneurons by neurotrophins: from development to cognitive disorders. Neuroscientist, February 1, 2006; 12(1): 43 - 56. [Abstract] [PDF]
|
|
|
|
 |
|
 H. P. Goodkin, J.-L. Yeh, and J. Kapur Status Epilepticus Increases the Intracellular Accumulation of GABAA Receptors J. Neurosci., June 8, 2005; 25(23): 5511 - 5520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Blum and A. Konnerth Neurotrophin-Mediated Rapid Signaling in the Central Nervous System: Mechanisms and Functions Physiology, February 1, 2005; 20(1): 70 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. A. Kramar, B. Lin, C.-Y. Lin, A. C. Arai, C. M. Gall, and G. Lynch A Novel Mechanism for the Facilitation of Theta-Induced Long-Term Potentiation by Brain-Derived Neurotrophic Factor J. Neurosci., June 2, 2004; 24(22): 5151 - 5161. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Jovanovic, P. Thomas, J. T. Kittler, T. G. Smart, and S. J. Moss Brain-Derived Neurotrophic Factor Modulates Fast Synaptic Inhibition by Regulating GABAA Receptor Phosphorylation, Activity, and Cell-Surface Stability J. Neurosci., January 14, 2004; 24(2): 522 - 530. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Mizoguchi, T. Kanematsu, M. Hirata, and J. Nabekura A Rapid Increase in the Total Number of Cell Surface Functional GABAA Receptors Induced by Brain-derived Neurotrophic Factor in Rat Visual Cortex J. Biol. Chem., November 7, 2003; 278(45): 44097 - 44102. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
