PT  - JOURNAL ARTICLE
AU  - Nicola Kuczewski
AU  - Christophe Porcher
AU  - Nadine Ferrand
AU  - Hervé Fiorentino
AU  - Christophe Pellegrino
AU  - Richard Kolarow
AU  - Volkmar Lessmann
AU  - Igor Medina
AU  - Jean-Luc Gaiarsa
TI  - Backpropagating Action Potentials Trigger Dendritic Release of BDNF during Spontaneous Network Activity
AID  - 10.1523/JNEUROSCI.1673-08.2008
DP  - 2008 Jul 02
TA  - The Journal of Neuroscience
PG  - 7013--7023
VI  - 28
IP  - 27
4099  - http://www.jneurosci.org/content/28/27/7013.short
4100  - http://www.jneurosci.org/content/28/27/7013.full
SO  - J. Neurosci.2008 Jul 02; 28
AB  - 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.