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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, Disks Large Homolog 4 Protein, 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