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Abstract:
BDNF plays a critical role in the regulation of synaptic strength and is essential for long-term potentiation, a phenomenon that underlies
learningandmemory.However,whetherBDNFactsinadiffusemanneroristargetedtospecificneuronalsubcompartmentsorsynaptic
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
axonsversusdendritesandarenotsharedbetweenthesecompartments.Moreover,syt-IV-andBDNF-harboringvesiclesarerecruitedto
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.
