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BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation, a phenomenon that underlies learning and memory. However, whether BDNF acts in a diffuse manner or is targeted to specific neuronal subcompartments or synaptic sites to affect circuit function remains unknown. Here, using photoactivation of BDNF or syt-IV (a regulator of exocytosis present on BDNF-containing vesicles) in transfected rat hippocampal neurons, we discovered that distinct subsets of BDNF vesicles are targeted to axons versus dendrites and are not shared between these compartments. Moreover, syt-IV- and BDNF-harboring vesicles are recruited to both presynaptic and postsynaptic sites in response to increased neuronal activity. Finally, using syt-IV knockout mouse neurons, we found that syt-IV is necessary for both presynaptic and postsynaptic scaling of synaptic strength in response to changes in network activity. These findings demonstrate that BDNF-containing vesicles can be targeted to specific sites in neurons and suggest that syt-IV-regulated BDNF secretion is subject to spatial control to regulate synaptic function in a site-specific manner.

Original publication




Journal article


J Neurosci

Publication Date





5398 - 5413


Activated-Leukocyte Cell Adhesion Molecule, Animals, Animals, Newborn, Axons, Brain-Derived Neurotrophic Factor, Cells, Cultured, Coculture Techniques, Colforsin, Dendrites, Embryo, Mammalian, Excitatory Amino Acid Agents, Excitatory Postsynaptic Potentials, Female, Glycine, Hippocampus, Humans, Intracellular Signaling Peptides and Proteins, Luminescent Proteins, Male, Membrane Proteins, Mice, Mice, Knockout, Microtubule-Associated Proteins, Neurons, Patch-Clamp Techniques, Rats, Receptors, AMPA, Sodium Channel Blockers, Synapses, Synaptic Vesicles, Synaptophysin, Synaptotagmins, Tetrodotoxin, Time Factors, Transfection, Vesicular Glutamate Transport Protein 1, Vesicular Inhibitory Amino Acid Transport Proteins