 |
Previous Article | Next Article 
The Journal of Neuroscience, September 1, 2002, 22(17):7580-7585
Brain-Derived Neurotrophic Factor Promotes the Maturation of
GABAergic Mechanisms in Cultured Hippocampal Neurons
Maki K.
Yamada*,
Kohsuke
Nakanishi*,
Shizu
Ohba,
Takeshi
Nakamura,
Yuji
Ikegaya,
Nobuyoshi
Nishiyama, and
Norio
Matsuki
Laboratory of Chemical Pharmacology, Graduate School of
Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo,
Bunkyo-ku, Tokyo 113-0033, Japan
Brain-derived neurotrophic factor (BDNF) has been implicated in
activity-dependent plasticity of neuronal function and network arrangement. To clarify how BDNF exerts its action, we evaluated the
physiological, histological, and biochemical characteristics of
cultured hippocampal neurons after long-term treatment with BDNF. Here
we show that BDNF facilitates high K+-elicited release of
GABA but not of glutamate and induces an increase in immunoreactive
signals of glutamic acid decarboxylase, a GABA-synthesizing enzyme. The
soma size of GABAergic neurons was enlarged in BDNF-treated cultures,
whereas the average soma size of all neurons was virtually unchanged.
BDNF also upregulated protein levels of GABAA receptors but
not of glutamate receptors. These data imply that BDNF selectively
advances the maturation of GABAergic synapses. However,
immunocytochemical analyses revealed that a significant expression of
TrkB, a high-affinity receptor for BDNF, was detected in non-GABAergic
as well as GABAergic neurons. BDNF also increased to total amount of
synaptic vesicle-associated proteins without affecting the number of
presynaptic vesicles that can be labeled with FM1-43 after
K+ depolarization. Together, our findings indicate
that BDNF principally promotes GABAergic maturation but may
also potentially contribute to excitatory synapse development via
increasing resting synaptic vesicles.
Key words:
Key word: BDNF; hippocampus; plasticity; neural network; GABA; inhibitory neuron; resting pool; synaptic vesicle-associated
protein
*
M.K.Y. and K.N. contributed equally to this work.
Copyright © 2002 Society for Neuroscience 0270-6474/02/22177580-06$05.00/0
This article has been cited by other articles:

|
 |

|
 |
 
H. M. Morris, T. Hashimoto, and D. A. Lewis
Alterations in Somatostatin mRNA Expression in the Dorsolateral Prefrontal Cortex of Subjects with Schizophrenia or Schizoaffective Disorder
Cereb Cortex,
July 1, 2008;
18(7):
1575 - 1587.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
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]
|
 |
|

|
 |

|
 |
 
E. Kumamaru, T. Numakawa, N. Adachi, Y. Yagasaki, A. Izumi, M. Niyaz, M. Kudo, and H. Kunugi
Glucocorticoid Prevents Brain-Derived Neurotrophic Factor-Mediated Maturation of Synaptic Function in Developing Hippocampal Neurons through Reduction in the Activity of Mitogen-Activated Protein Kinase
Mol. Endocrinol.,
March 1, 2008;
22(3):
546 - 558.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
L. Medrihan, E. Tantalaki, G. Aramuni, V. Sargsyan, I. Dudanova, M. Missler, and W. Zhang
Early Defects of GABAergic Synapses in the Brain Stem of a MeCP2 Mouse Model of Rett Syndrome
J Neurophysiol,
January 1, 2008;
99(1):
112 - 121.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. L. Payne, W. M. Connelly, J. H. Ives, R. Lehner, B. Furtmuller, W. Sieghart, P. Tiwari, J. M. Lucocq, G. Lees, and C. L. Thompson
GABAA {alpha}6-Containing Receptors Are Selectively Compromised in Cerebellar Granule Cells of the Ataxic Mouse, Stargazer
J. Biol. Chem.,
October 5, 2007;
282(40):
29130 - 29143.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Kolarow, T. Brigadski, and V. Lessmann
Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening
J. Neurosci.,
September 26, 2007;
27(39):
10350 - 10364.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Kohara, H. Yasuda, Y. Huang, N. Adachi, K. Sohya, and T. Tsumoto
A Local Reduction in Cortical GABAergic Synapses after a Loss of Endogenous Brain-Derived Neurotrophic Factor, as Revealed by Single-Cell Gene Knock-Out Method
J. Neurosci.,
July 4, 2007;
27(27):
7234 - 7244.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Yamada, K. Tanemura, S. Okada, A. Iwanami, M. Nakamura, H. Mizuno, M. Ozawa, R. Ohyama-Goto, N. Kitamura, M. Kawano, et al.
Electrical Stimulation Modulates Fate Determination of Differentiating Embryonic Stem Cells
Stem Cells,
March 1, 2007;
25(3):
562 - 570.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. Sahun, J. M. Delgado-Garcia, A. Amador-Arjona, A. Giralt, J. Alberch, M. Dierssen, and A. Gruart
Dissociation between CA3-CA1 Synaptic Plasticity and Associative Learning in TgNTRK3 Transgenic Mice
J. Neurosci.,
February 28, 2007;
27(9):
2253 - 2260.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. A. Gomes, C. Hampton, F. El-Sabeawy, S. L. Sabo, and A. K. McAllister
The Dynamic Distribution of TrkB Receptors before, during, and after Synapse Formation between Cortical Neurons.
J. Neurosci.,
November 1, 2006;
26(44):
11487 - 11500.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. L. Payne, P. S. Donoghue, W. M. K. Connelly, S. Hinterreiter, P. Tiwari, J. H. Ives, V. Hann, W. Sieghart, G. Lees, and C. L. Thompson
Aberrant GABAA Receptor Expression in the Dentate Gyrus of the Epileptic Mutant Mouse Stargazer.
J. Neurosci.,
August 15, 2006;
26(33):
8600 - 8608.
[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]
|
 |
|

|
 |

|
 |
 
M. A. Carmona, E. Pozas, A. Martinez, J. F. Espinosa-Parrilla, E. Soriano, and F. Aguado
Age-dependent Spontaneous Hyperexcitability and Impairment of GABAergic Function in the Hippocampus of Mice Lacking trkB
Cereb Cortex,
January 1, 2006;
16(1):
47 - 63.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Koyama and Y. Ikegaya
To BDNF or Not to BDNF: That Is the Epileptic Hippocampus
Neuroscientist,
August 1, 2005;
11(4):
282 - 287.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Gomez-Lira, M. Lamas, H. Romo-Parra, and R. Gutierrez
Programmed and Induced Phenotype of the Hippocampal Granule Cells
J. Neurosci.,
July 27, 2005;
25(30):
6939 - 6946.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. B. Elmariah, E. J. Oh, E. G. Hughes, and R. J. Balice-Gordon
Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABAA Receptors
J. Neurosci.,
April 6, 2005;
25(14):
3638 - 3650.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Baldelli, J.-M. Hernandez-Guijo, V. Carabelli, and E. Carbone
Brain-Derived Neurotrophic Factor Enhances GABA Release Probability and Nonuniform Distribution of N- and P/Q-Type Channels on Release Sites of Hippocampal Inhibitory Synapses
J. Neurosci.,
March 30, 2005;
25(13):
3358 - 3368.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Ohba, T. Ikeda, Y. Ikegaya, N. Nishiyama, N. Matsuki, and M. K. Yamada
BDNF Locally Potentiates GABAergic Presynaptic Machineries: Target-selective Circuit Inhibition
Cereb Cortex,
March 1, 2005;
15(3):
291 - 298.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Hashimoto, S. E. Bergen, Q. L. Nguyen, B. Xu, L. M. Monteggia, J. N. Pierri, Z. Sun, A. R. Sampson, and D. A. Lewis
Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia
J. Neurosci.,
January 12, 2005;
25(2):
372 - 383.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Coleman, H. Federoff, and R. Kurlan
A focus on the synapse for neuroprotection in Alzheimer disease and other dementias
Neurology,
October 12, 2004;
63(7):
1155 - 1162.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. Koyama, M. K. Yamada, S. Fujisawa, R. Katoh-Semba, N. Matsuki, and Y. Ikegaya
Brain-Derived Neurotrophic Factor Induces Hyperexcitable Reentrant Circuits in the Dentate Gyrus
J. Neurosci.,
August 18, 2004;
24(33):
7215 - 7224.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. B. Elmariah, M. A. Crumling, T. D. Parsons, and R. J. Balice-Gordon
Postsynaptic TrkB-Mediated Signaling Modulates Excitatory and Inhibitory Neurotransmitter Receptor Clustering at Hippocampal Synapses
J. Neurosci.,
March 10, 2004;
24(10):
2380 - 2393.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Fujisawa, M. K. Yamada, N. Nishiyama, N. Matsuki, and Y. Ikegaya
BDNF Boosts Spike Fidelity in Chaotic Neural Oscillations
Biophys. J.,
March 1, 2004;
86(3):
1820 - 1828.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Hayashi, R. Kawai-Hirai, A. Harada, and K. Takata
Inhibitory neurons from fetal rat cerebral cortex exert delayed axon formation and active migration in vitro
J. Cell Sci.,
November 1, 2003;
116(21):
4419 - 4428.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Kohara, A. Kitamura, N. Adachi, M. Nishida, C. Itami, S. Nakamura, and T. Tsumoto
Inhibitory But Not Excitatory Cortical Neurons Require Presynaptic Brain-Derived Neurotrophic Factor for Dendritic Development, as Revealed by Chimera Cell Culture
J. Neurosci.,
July 9, 2003;
23(14):
6123 - 6131.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Jin, H. Hu, P. H. Mathers, and A. Agmon
Brain-Derived Neurotrophic Factor Mediates Activity-Dependent Dendritic Growth in Nonpyramidal Neocortical Interneurons in Developing Organotypic Cultures
J. Neurosci.,
July 2, 2003;
23(13):
5662 - 5673.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Yokomaku, T. Numakawa, Y. Numakawa, S. Suzuki, T. Matsumoto, N. Adachi, C. Nishio, T. Taguchi, and H. Hatanaka
Estrogen Enhances Depolarization-Induced Glutamate Release through Activation of Phosphatidylinositol 3-Kinase and Mitogen-Activated Protein Kinase in Cultured Hippocampal Neurons
Mol. Endocrinol.,
May 1, 2003;
17(5):
831 - 844.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|