Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 291 (5512): 2419-2423

Copyright © 2001 by the American Association for the Advancement of Science

Activity-Dependent Transfer of Brain-Derived Neurotrophic Factor to Postsynaptic Neurons

Keigo Kohara, Akihiko Kitamura, Mieko Morishima, Tadaharu Tsumoto*

Neurotrophins such as brain-derived neurotrophic factor (BDNF) are thought to be transferred from post- to presynaptic neurons and to be involved in the formation and plasticity of neural circuits. However, direct evidence for a transneuronal transfer of BDNF and its relation to neuronal activity remains elusive. We simultaneously injected complementary DNAs of green fluorescent protein (GFP)-tagged BDNF and red fluorescence protein into the nucleus of single neurons and visualized expression, localization, and transport of BDNF in living neurons. Fluorescent puncta representing BDNF moved in axons in the anterograde direction, though some moved retrogradely, and transferred to postsynaptic neurons in an activity-dependent manner.

Division of Neurophysiology, Biomedical Research Center, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871 Japan, and CREST, Japan Science and Technology Corporation, 1-8, Honcho 4-chome, Kawaguchi, 332-0012, Japan.
*   To whom correspondence should be addressed. E-mail: ttsumoto{at}

Spike-timing-dependent BDNF secretion and synaptic plasticity.
H. Lu, H. Park, and M.-M. Poo (2013)
Phil Trans R Soc B 369, 20130132
   Abstract »    Full Text »    PDF »
{beta}-Amyloid (A{beta}) Oligomers Impair Brain-derived Neurotrophic Factor Retrograde Trafficking by Down-regulating Ubiquitin C-terminal Hydrolase, UCH-L1.
W. W. Poon, A. J. Carlos, B. L. Aguilar, N. C. Berchtold, C. K. Kawano, V. Zograbyan, T. Yaopruke, M. Shelanski, and C. W. Cotman (2013)
J. Biol. Chem. 288, 16937-16948
   Abstract »    Full Text »    PDF »
Phencyclidine-Induced Decrease of Synaptic Connectivity via Inhibition of BDNF Secretion in Cultured Cortical Neurons.
N. Adachi, T. Numakawa, E. Kumamaru, C. Itami, S. Chiba, Y. Iijima, M. Richards, R. Katoh-Semba, and H. Kunugi (2013)
Cereb Cortex 23, 847-858
   Abstract »    Full Text »    PDF »
Enhanced GABAergic Activity in the Mouse Primary Somatosensory Cortex Is Insufficient to Alleviate Chronic Pain Behavior with Reduced Expression of Neuronal Potassium-Chloride Cotransporter.
K. Eto, H. Ishibashi, T. Yoshimura, M. Watanabe, A. Miyamoto, K. Ikenaka, A. J. Moorhouse, and J. Nabekura (2012)
J. Neurosci. 32, 16552-16559
   Abstract »    Full Text »    PDF »
Distinct Subsets of Syt-IV/BDNF Vesicles Are Sorted to Axons versus Dendrites and Recruited to Synapses by Activity.
C. Dean, H. Liu, T. Staudt, M. A. Stahlberg, S. Vingill, J. Buckers, D. Kamin, J. Engelhardt, M. B. Jackson, S. W. Hell, et al. (2012)
J. Neurosci. 32, 5398-5413
   Abstract »    Full Text »    PDF »
Dendritic SNAREs add a new twist to the old neuron theory.
S. V. Ovsepian and J. O. Dolly (2011)
PNAS 108, 19113-19120
   Abstract »    Full Text »    PDF »
The Locus Ceruleus Responds to Signaling Molecules Obtained from the CSF by Transfer through Tanycytes.
C.-Y. Feng, L. M. Wiggins, and C. S. von Bartheld (2011)
J. Neurosci. 31, 9147-9158
   Abstract »    Full Text »    PDF »
Dynamic Imaging of Axonal Transport in Living Retinal Ganglion Cells In Vitro.
Y. Takihara, M. Inatani, H. Hayashi, N. Adachi, K. Iwao, T. Inoue, M. Iwao, and H. Tanihara (2011)
Invest. Ophthalmol. Vis. Sci. 52, 3039-3045
   Abstract »    Full Text »    PDF »
Antibody to Varicella-Zoster Virus Immediate-Early Protein 62 Augments Allodynia in Zoster via Brain-Derived Neurotrophic Factor.
Y. Hama, K. Shiraki, Y. Yoshida, A. Maruyama, M. Yasuda, M. Tsuda, M. Honda, M. Takahashi, H. Higuchi, I. Takasaki, et al. (2010)
J. Virol. 84, 1616-1624
   Abstract »    Full Text »    PDF »
Differential Activity-Dependent Secretion of Brain-Derived Neurotrophic Factor from Axon and Dendrite.
N. Matsuda, H. Lu, Y. Fukata, J. Noritake, H. Gao, S. Mukherjee, T. Nemoto, M. Fukata, and M.-m. Poo (2009)
J. Neurosci. 29, 14185-14198
   Abstract »    Full Text »    PDF »
A Single Intra-PFC Infusion of BDNF Prevents Cocaine-Induced Alterations in Extracellular Glutamate within the Nucleus Accumbens.
W. J. Berglind, T. W. Whitfield Jr, R. T. LaLumiere, P. W. Kalivas, and J. F. McGinty (2009)
J. Neurosci. 29, 3715-3719
   Abstract »    Full Text »    PDF »
Spontaneous glutamatergic activity induces a BDNF-dependent potentiation of GABAergic synapses in the newborn rat hippocampus.
N. Kuczewski, A. Langlois, H. Fiorentino, S. Bonnet, T. Marissal, D. Diabira, N. Ferrand, C. Porcher, and J.-L. Gaiarsa (2008)
J. Physiol. 586, 5119-5128
   Abstract »    Full Text »    PDF »
Chronic Fatigue Syndrome and the Central Nervous System.
R. Chen, F. Liang, J. Moriya, J. Yamakawa, H. Sumino, T. Kanda, and T. Takahashi (2008)
Journal of International Medical Research 36, 867-874
   Abstract »    PDF »
Roles of Endocannabinoids in Heterosynaptic Long-Term Depression of Excitatory Synaptic Transmission in Visual Cortex of Young Mice.
Y. Huang, H. Yasuda, A. Sarihi, and T. Tsumoto (2008)
J. Neurosci. 28, 7074-7083
   Abstract »    Full Text »    PDF »
Neurotrophin-Dependent Dendritic Filopodial Motility: A Convergence on PI3K Signaling.
B. W. Luikart, W. Zhang, G. A. Wayman, C.-H. Kwon, G. L. Westbrook, and L. F. Parada (2008)
J. Neurosci. 28, 7006-7012
   Abstract »    Full Text »    PDF »
Steroid Hormones Act Transsynaptically within the Forebrain to Regulate Neuronal Phenotype and Song Stereotypy.
J. Meitzen, I. T. Moore, K. Lent, E. A. Brenowitz, and D. J. Perkel (2007)
J. Neurosci. 27, 12045-12057
   Abstract »    Full Text »    PDF »
Disruption of a novel regulatory locus results in decreased Bdnf expression, obesity, and type 2 diabetes in mice.
H. Sha, J. Xu, J. Tang, J. Ding, J. Gong, X. Ge, D. Kong, and X. Gao (2007)
Physiol Genomics 31, 252-263
   Abstract »    Full Text »    PDF »
Postsynaptic Secretion of BDNF and NT-3 from Hippocampal Neurons Depends on Calcium Calmodulin Kinase II Signaling and Proceeds via Delayed Fusion Pore Opening.
R. Kolarow, T. Brigadski, and V. Lessmann (2007)
J. Neurosci. 27, 10350-10364
   Abstract »    Full Text »    PDF »
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.
K. Kohara, H. Yasuda, Y. Huang, N. Adachi, K. Sohya, and T. Tsumoto (2007)
J. Neurosci. 27, 7234-7244
   Abstract »    Full Text »    PDF »
Miniature Synaptic Currents Become Neurotoxic to Chronically Silenced Neurons.
I. Fishbein and M. Segal (2007)
Cereb Cortex 17, 1292-1306
   Abstract »    Full Text »    PDF »
Histone Deacetylase 6 Inhibition Compensates for the Transport Deficit in Huntington's Disease by Increasing Tubulin Acetylation.
J. P. Dompierre, J. D. Godin, B. C. Charrin, F. P. Cordelieres, S. J. King, S. Humbert, and F. Saudou (2007)
J. Neurosci. 27, 3571-3583
   Abstract »    Full Text »    PDF »
Endogenous Brain-Derived Neurotrophic Factor Triggers Fast Calcium Transients at Synapses in Developing Dendrites.
S. B. Lang, V. Stein, T. Bonhoeffer, and C. Lohmann (2007)
J. Neurosci. 27, 1097-1105
   Abstract »    Full Text »    PDF »
Single-Cell Characterization of Retrograde Signaling by Brain-Derived Neurotrophic Factor.
J. P. Magby, C. Bi, Z.-Y. Chen, F. S. Lee, and M. R. Plummer (2006)
J. Neurosci. 26, 13531-13536
   Abstract »    Full Text »    PDF »
Plasticity Compartments in Basal Dendrites of Neocortical Pyramidal Neurons.
U. Gordon, A. Polsky, and J. Schiller (2006)
J. Neurosci. 26, 12717-12726
   Abstract »    Full Text »    PDF »
Mutant huntingtin Impairs the Post-Golgi Trafficking of Brain-Derived Neurotrophic Factor But Not Its Val66Met Polymorphism.
D. del Toro, J. M. Canals, S. Gines, M. Kojima, G. Egea, and J. Alberch (2006)
J. Neurosci. 26, 12748-12757
   Abstract »    Full Text »    PDF »
The Dynamic Distribution of TrkB Receptors before, during, and after Synapse Formation between Cortical Neurons..
R. A. Gomes, C. Hampton, F. El-Sabeawy, S. L. Sabo, and A. K. McAllister (2006)
J. Neurosci. 26, 11487-11500
   Abstract »    Full Text »    PDF »
Sprouting, regeneration and circuit formation in the injured spinal cord: factors and activity.
I. C Maier and M. E Schwab (2006)
Phil Trans R Soc B 361, 1611-1634
   Abstract »    Full Text »    PDF »
Hippocampal neurons recycle BDNF for activity-dependent secretion and LTP maintenance.
S. Santi, S. Cappello, M. Riccio, M. Bergami, G. Aicardi, U. Schenk, M. Matteoli, and M. Canossa (2006)
EMBO J. 25, 4372-4380
   Abstract »    Full Text »    PDF »
Preconditioning doses of NMDA promote neuroprotection by enhancing neuronal excitability..
F. X. Soriano, S. Papadia, F. Hofmann, N. R. Hardingham, H. Bading, and G. E. Hardingham (2006)
J. Neurosci. 26, 4509-4518
   Abstract »    Full Text »    PDF »
Hippocampal long-term potentiation is supported by presynaptic and postsynaptic tyrosine receptor kinase B-mediated phospholipase Cgamma signaling..
A. Gartner, D. G. Polnau, V. Staiger, C. Sciarretta, L. Minichiello, H. Thoenen, T. Bonhoeffer, and M. Korte (2006)
J. Neurosci. 26, 3496-3504
   Abstract »    Full Text »    PDF »
Differential Vesicular Targeting and Time Course of Synaptic Secretion of the Mammalian Neurotrophins.
T. Brigadski, M. Hartmann, and V. Lessmann (2005)
J. Neurosci. 25, 7601-7614
   Abstract »    Full Text »    PDF »
Regulation of brain-derived neurotrophic factor (BDNF) during sleep apnoea treatment.
R Staats, P Stoll, D Zingler, J C Virchow, and M Lommatzsch (2005)
Thorax 60, 688-692
   Abstract »    Full Text »    PDF »
TrkB Has a Cell-Autonomous Role in the Establishment of Hippocampal Schaffer Collateral Synapses.
B. W. Luikart, S. Nef, T. Virmani, M. E. Lush, Y. Liu, E. T. Kavalali, and L. F. Parada (2005)
J. Neurosci. 25, 3774-3786
   Abstract »    Full Text »    PDF »
Astrocytes Regulate Inhibitory Synapse Formation via Trk-Mediated Modulation of Postsynaptic GABAA Receptors.
S. B. Elmariah, E. J. Oh, E. G. Hughes, and R. J. Balice-Gordon (2005)
J. Neurosci. 25, 3638-3650
   Abstract »    Full Text »    PDF »
Activity-dependent maintenance and growth of dendrites in adult cortex.
C. Tailby, L. L. Wright, A. B. Metha, and M. B. Calford (2005)
PNAS 102, 4631-4636
   Abstract »    Full Text »    PDF »
Transcellular induction of neuropeptide Y expression by NT4 and BDNF.
M. J. Wirth, S. Patz, and P. Wahle (2005)
PNAS 102, 3064-3069
   Abstract »    Full Text »    PDF »
Hippocampal Synaptic Modulation by the Phosphotyrosine Adapter Protein ShcC/N-Shc via Interaction with the NMDA Receptor.
Y. Miyamoto, L. Chen, M. Sato, M. Sokabe, T. Nabeshima, T. Pawson, R. Sakai, and N. Mori (2005)
J. Neurosci. 25, 1826-1835
   Abstract »    Full Text »    PDF »
A Truncated Tropo-Myosine-Related Kinase B Receptor, T1, Regulates Glial Cell Morphology via Rho GDP Dissociation Inhibitor 1.
K. Ohira, H. Kumanogoh, Y. Sahara, K. J. Homma, H. Hirai, S. Nakamura, and M. Hayashi (2005)
J. Neurosci. 25, 1343-1353
   Abstract »    Full Text »    PDF »
Neurotrophin-Mediated Rapid Signaling in the Central Nervous System: Mechanisms and Functions.
R. Blum and A. Konnerth (2005)
Physiology 20, 70-78
   Abstract »    Full Text »    PDF »
Brain-Derived Neurotrophic Factor Induces Mammalian Target of Rapamycin-Dependent Local Activation of Translation Machinery and Protein Synthesis in Neuronal Dendrites.
N. Takei, N. Inamura, M. Kawamura, H. Namba, K. Hara, K. Yonezawa, and H. Nawa (2004)
J. Neurosci. 24, 9760-9769
   Abstract »    Full Text »    PDF »
Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor.
G. Aicardi, E. Argilli, S. Cappello, S. Santi, M. Riccio, H. Thoenen, and M. Canossa (2004)
PNAS 101, 15788-15792
   Abstract »    Full Text »    PDF »
A focus on the synapse for neuroprotection in Alzheimer disease and other dementias.
P. Coleman, H. Federoff, and R. Kurlan (2004)
Neurology 63, 1155-1162
   Abstract »    Full Text »    PDF »
Brain-Derived Neurotrophic Factor Induces Hyperexcitable Reentrant Circuits in the Dentate Gyrus.
R. Koyama, M. K. Yamada, S. Fujisawa, R. Katoh-Semba, N. Matsuki, and Y. Ikegaya (2004)
J. Neurosci. 24, 7215-7224
   Abstract »    Full Text »    PDF »
Postsynaptic TrkB-Mediated Signaling Modulates Excitatory and Inhibitory Neurotransmitter Receptor Clustering at Hippocampal Synapses.
S. B. Elmariah, M. A. Crumling, T. D. Parsons, and R. J. Balice-Gordon (2004)
J. Neurosci. 24, 2380-2393
   Abstract »    Full Text »    PDF »
Environmental Enrichment Rescues Protein Deficits in a Mouse Model of Huntington's Disease, Indicating a Possible Disease Mechanism.
T. L. Spires, H. E. Grote, N. K. Varshney, P. M. Cordery, A. van Dellen, C. Blakemore, and A. J. Hannan (2004)
J. Neurosci. 24, 2270-2276
   Abstract »    Full Text »    PDF »
The Secretory Granule-Associated Protein CAPS2 Regulates Neurotrophin Release and Cell Survival.
T. Sadakata, A. Mizoguchi, Y. Sato, R. Katoh-Semba, M. Fukuda, K. Mikoshiba, and T. Furuichi (2004)
J. Neurosci. 24, 43-52
   Abstract »    Full Text »    PDF »
Accelerated dendritic development of rat cortical pyramidal cells and interneurons after biolistic transfection with BDNF and NT4/5.
M. J. Wirth, A. Brun, J. Grabert, S. Patz, and P. Wahle (2003)
Development 130, 5827-5838
   Abstract »    Full Text »    PDF »
Neurotrophin-4, Alone or Heterodimerized with Brain-derived Neurotrophic Factor, Is Sorted to the Constitutive Secretory Pathway.
A. P. Hibbert, S. J. Morris, N. G. Seidah, and R. A. Murphy (2003)
J. Biol. Chem. 278, 48129-48136
   Abstract »    Full Text »    PDF »
Brain-derived neurotrophic factor-dependent unmasking of "silent" synapses in the developing mouse barrel cortex.
C. Itami, F. Kimura, T. Kohno, M. Matsuoka, M. Ichikawa, T. Tsumoto, and S. Nakamura (2003)
PNAS 100, 13069-13074
   Abstract »    Full Text »    PDF »
Synaptogenesis in the CNS: An Odyssey from Wiring Together to Firing Together.
D. W Munno and N. I Syed (2003)
J. Physiol. 552, 1-11
   Abstract »    Full Text »    PDF »
Inhibitory But Not Excitatory Cortical Neurons Require Presynaptic Brain-Derived Neurotrophic Factor for Dendritic Development, as Revealed by Chimera Cell Culture.
K. Kohara, A. Kitamura, N. Adachi, M. Nishida, C. Itami, S. Nakamura, and T. Tsumoto (2003)
J. Neurosci. 23, 6123-6131
   Abstract »    Full Text »    PDF »
Brain-Derived Neurotrophic Factor Mediates Activity-Dependent Dendritic Growth in Nonpyramidal Neocortical Interneurons in Developing Organotypic Cultures.
X. Jin, H. Hu, P. H. Mathers, and A. Agmon (2003)
J. Neurosci. 23, 5662-5673
   Abstract »    Full Text »    PDF »
The action of BDNF on GABAA currents changes from potentiating to suppressing during maturation of rat hippocampal CA1 pyramidal neurons.
Y. Mizoguchi, H. Ishibashi, and J. Nabekura (2003)
J. Physiol. 548, 703-709
   Abstract »    Full Text »    PDF »
How does an axon grow?.
J. L. Goldberg (2003)
Genes & Dev. 17, 941-958
   Full Text »    PDF »
BDNF regulates spontaneous correlated activity at early developmental stages by increasing synaptogenesis and expression of the K+/Cl- co-transporter KCC2.
F. Aguado, M. A. Carmona, E. Pozas, A. Aguilo, F. J. Martinez-Guijarro, S. Alcantara, V. Borrell, R. Yuste, C. F. Ibanez, and E. Soriano (2003)
Development 130, 1267-1280
   Abstract »    Full Text »    PDF »
Differential effects of cortical neurotrophic factors on development of lateral geniculate nucleus and superior colliculus neurons: anterograde and retrograde actions.
P. Wahle, G. Di Cristo, G. Schwerdtfeger, M. Engelhardt, N. Berardi, and L. Maffei (2003)
Development 130, 611-622
   Abstract »    Full Text »    PDF »
The Role of Neurotrophins in Neurotransmitter Release.
W. J. Tyler, S. P. Perrett, and L. D. Pozzo-Miller (2002)
Neuroscientist 8, 524-531
   Abstract »    PDF »
Cellular Mechanisms Regulating Activity-Dependent Release of Native Brain-Derived Neurotrophic Factor from Hippocampal Neurons.
A. Balkowiec and D. M. Katz (2002)
J. Neurosci. 22, 10399-10407
   Abstract »    Full Text »    PDF »
Regulation of TRKB Surface Expression by Brain-derived Neurotrophic Factor and Truncated TRKB Isoforms.
A. Haapasalo, I. Sipola, K. Larsson, K. E. O. Akerman, P. Stoilov, S. Stamm, G. Wong, and E. Castren (2002)
J. Biol. Chem. 277, 43160-43167
   Abstract »    Full Text »    PDF »
Brain-derived Neurotrophic Factor Regulates Surface Expression of {alpha}-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic Acid Receptors by Enhancing the N-Ethylmaleimide-sensitive Factor/GluR2 Interaction in Developing Neocortical Neurons.
M. Narisawa-Saito, Y. Iwakura, M. Kawamura, K. Araki, S. Kozaki, N. Takei, and H. Nawa (2002)
J. Biol. Chem. 277, 40901-40910
   Abstract »    Full Text »    PDF »
Motoneuron-Derived Neurotrophin-3 Is a Survival Factor for PAX2-Expressing Spinal Interneurons.
C. Bechade, C. Mallecourt, F. Sedel, S. Vyas, and A. Triller (2002)
J. Neurosci. 22, 8779-8784
   Abstract »    Full Text »    PDF »
Act locally and think globally: Intracerebral testosterone implants induce seasonal-like growth of adult avian song control circuits.
E. A. Brenowitz and K. Lent (2002)
PNAS 99, 12421-12426
   Abstract »    Full Text »    PDF »
From Acquisition to Consolidation: On the Role of Brain-Derived Neurotrophic Factor Signaling in Hippocampal-Dependent Learning.
W. J. Tyler, M. Alonso, C. R. Bramham, and L. D. Pozzo-Miller (2002)
Learn. Mem. 9, 224-237
   Abstract »    Full Text »    PDF »
Brain-Derived Neurotrophic Factor Is Essential for Opiate-Induced Plasticity of Noradrenergic Neurons.
S. Akbarian, M. Rios, R.-J. Liu, S. J. Gold, H.-F. Fong, S. Zeiler, V. Coppola, L. Tessarollo, K. R. Jones, E. J. Nestler, et al. (2002)
J. Neurosci. 22, 4153-4162
   Abstract »    Full Text »    PDF »
The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes.
Y. Yin, G. M. Edelman, and P. W. Vanderklish (2002)
PNAS 99, 2368-2373
   Abstract »    Full Text »    PDF »
Regional Differences in Neurotrophin Availability Regulate Selective Expression of VGF in the Developing Limbic Cortex.
K. L. Eagleson, L. D. Fairfull, S. R. J. Salton, and P. Levitt (2001)
J. Neurosci. 21, 9315-9324
   Abstract »    Full Text »    PDF »
Synaptic secretion of BDNF after high-frequency stimulation of glutamatergic synapses.
M. Hartmann, R. Heumann, and V. Lessmann (2001)
EMBO J. 20, 5887-5897
   Abstract »    Full Text »    PDF »
Neurotrophins: Which Way Did They Go?.
R. Segal (2001)
Sci. STKE 2001, pe1
   Abstract »    Full Text »    PDF »
The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes.
Y. Yin, G. M. Edelman, and P. W. Vanderklish (2002)
PNAS 99, 2368-2373
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882