Fig. 8.

A diagram illustrating the secretion, uptake, and trafficking of BDNF at excitatory synapses. Post-Golgi granules containing BDNF are known to be the major source of BDNF secreted at the synapse. Binding of secreted BDNF to TrkB receptor leads to endocytic uptake of BDNF-TrkB complexes into “signaling endosomes” by either pre- or postsynaptic neuron. Synaptic activation could result in the exocytosis of not only BDNF-containing granules, but also endosomes containing endocytosed BDNF, in a manner requiring the activation of synaptic AMPA and NMDA receptors. Distinct from the Syt4 that is required for exocytosis of BDNF-containing post-Golgi granules, Syt6 is essential for activity-induced exocytosis of BDNF-containing endosomes. Endocytosed BDNF at postsynaptic dendrites may undergo local exocytosis for reuse near the uptake sites, whereas BDNF-containing endosomes formed by axonal terminals may undergo long-range retrograde transport to somatic and dendritic sites of the presynaptic neuron.