Backpropagating action potentials trigger dendritic release of BDNF during spontaneous network activity.
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.
Kuczewski
Nicola
N
Institut de Neurobiologie de la Méditerranée, Inserm Unité 901 and Université de La Méditerranée, 13273 Marseille Cedex 09, France.
Porcher
Christophe
C
Ferrand
Nadine
N
Fiorentino
Hervé
H
Pellegrino
Christophe
C
Kolarow
Richard
R
Lessmann
Volkmar
V
Medina
Igor
I
Gaiarsa
Jean-Luc
JL
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics; D017781:Genes, Immediate-Early / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000254:growth & development*; D007150:Immunohistochemistry; D009415:Nerve Net / Q000254:growth & development*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D010766:Phosphorylation; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013194:Staining and Labeling; D009435:Synaptic Transmission / Q000502:physiology; D015533:Transcriptional Activation
D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins