Distinct Subsets of Syt-IV/BDNF Vesicles Are Sorted to Axons versus Dendrites and Recruited to Synapses by Activity

BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation (LTP), a phenomenon that underlies learning and memory. However, whether BDNF acts in a diffuse manner, or is targeted to specific neuronal sub-compartments 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 pre and post-synaptic sites in response to increased neuronal activity. Finally, using syt-IV knockout mouse neurons, we found that syt-IV is necessary for both pre- and post-synaptic 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.