Neuronal activity enhances Brain-Derived Neurotrophic Factor local signaling in axon through modifying its axonal transport

This dissertation, by Zheng Zeng, explores a role for neuronal activity in modulating brain-derived neurotrophic factor (BDNF) signaling in axons. BDNF gene expression and release are modulated by activity and, correspondingly, BDNF serves to mediate several facets activity-dependent neuronal adaptation, including changes in neuronal structure and function. Remarkably little is known of what effect activity may have on BDNF signaling and function in axons. I employed microfluidic devices, in vitro neuronal activation, live imaging and biochemical methods to show that activation of neurons reduced the speed and net flux of BDNF retrograde transport in axons with a resulting increase in the robustness of BDNF signaling in this compartment. My findings set the stage for studies to explore the mechanism by which neuronal activity impacts BDNF transport and the biological consequences of increased signaling in axons