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The Journal of Neuroscience, July 2, 2008, 28(27):7013-7023; doi:10.1523/JNEUROSCI.1673-08.2008

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 Previous Article

Development/Plasticity/Repair
Backpropagating Action Potentials Trigger Dendritic Release of BDNF during Spontaneous Network Activity

Nicola Kuczewski,¹ Christophe Porcher,¹ Nadine Ferrand,¹ Hervé Fiorentino,¹ Christophe Pellegrino,¹ Richard Kolarow,² Volkmar Lessmann,² Igor Medina,¹ and Jean-Luc Gaiarsa¹

¹Institut de Neurobiologie de la Méditerranée, Inserm Unité 901 and Université de La Méditerranée, 13273 Marseille Cedex 09, France, and ²Institute of Physiology, Otto-von-Guericke-University Magdeburg, 39120 Magdeburg, Germany

Correspondence should be addressed to Nicola Kuczewski, Institut de Neurobiologie de la Méditerranée, Inserm Unité 901, Parc Scientifique de Luminy, BP 13, 13273 Marseille Cedex 9, France. Email: kuczewski{at}inmed.univ-mrs.fr

Brain-derived neurotrophic factor (BDNF) is a major regulator of activity-dependent synapse development and plasticity. Because BDNF is a secreted protein, it has been proposed that BDNF is released from target neurons in an activity-dependent manner. However, direct evidence for postsynaptic release of BDNF triggered by ongoing network activity is still lacking. Here we transfected cultures of dissociated hippocampal neurons with green fluorescent protein (GFP)-tagged BDNF and combined whole-cell recording, time-lapse fluorescent imaging, and immunostaining to monitor activity-dependent dendritic release of BDNF. We found that spontaneous backpropagating action potentials, but not synaptic activity alone, led to a Ca²⁺-dependent dendritic release of BDNF-GFP. Moreover, we provide evidence that endogenous BDNF released from a single neuron can phosphorylate CREB (cAMP response element-binding protein) in neighboring neurons, an important step of immediate early gene activation. Therefore, together, our results support the hypothesis that BDNF might act as a target-derived messenger of activity-dependent synaptic plasticity and development.

Key words: BDNF; synaptic plasticity; LTP; development; action potential; neurotrophins

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Received Dec. 21, 2007; revised May 26, 2008; accepted June 2, 2008.

Correspondence should be addressed to Nicola Kuczewski, Institut de Neurobiologie de la Méditerranée, Inserm Unité 901, Parc Scientifique de Luminy, BP 13, 13273 Marseille Cedex 9, France. Email: kuczewski{at}inmed.univ-mrs.fr

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