Pre-synaptic TrkB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction

Brain-derived neurotrophic factor (BDNF) and its high affinity receptor, TrkB, play an essential role in memory extinction. Our previous work has shown that JIP3 (JNK interacted protein 3) mediates anterograde axonal transport of TrkB through the direct binding of its coiled-coil domain 1 (CC1) with TrkB. Here, we constructed a fluorescent CC1 and enhanced green fluorescent protein (EGFP) fused protein, CC1-EGFP, and found that CC1-EGFP could specifically interrupt TrkB anterograde axonal transport and its localization at the pre-synaptic site. Consistent with this, TrkB-mediated pre-synaptic vesicle release and retrograde axonal signaling transmission were disrupted by CC1-EGFP. Neuronal expression of CC1-EGFP in the basolateral amygdala (BLA) impaired fear memory extinction. And, it blocked BDNF in the BLA-induced enhancement of TrkB phosphorylation in the infralimbic prefrontal cortex (IL). Together, this study not only suggests that pre-synaptic TrkB in BLA neurons is necessary for memory extinction and contributes to the BDNF signaling transduction from the BLA to IL, but also provides CC1-EGFP as a novel tool to specifically regulate pre-synaptic TrkB expression in vitro and in vivo.