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Dev Neurobiol. 2018 Jul;78(7):647-659. doi: 10.1002/dneu.22592. Epub 2018 Mar 31.

Differential effects of transient and sustained activation of BDNF-TrkB signaling.

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School of Pharmaceutical Sciences, IDG/McGovern Institute for Brain Research, Tsinghua University, Beijing, 100084, China.
R&D Center for the Diagnosis and Treatment of Major Brain Diseases, Research Institute of Tsinghua University in Shenzhen, Shenzhen, Guandong, 518057, China.
GlaxoSmithKline, R&D China, Shanghai, 201203, China.


Brain-derived neurotrophic factor (BDNF) serves a pleiotropic role in the central nervous system, ranging from promoting neuronal survival and differentiation during development and synaptic modulation in the adult. An important, yet unanswered question is how BDNF could serve such diverse functions, sometimes in the same cell. At least two modes of BDNF actions have been elucidated so far based on BDNF signaling kinetics and/or the activity status of the responding neurons. Acute and gradual increases in extracellular BDNF concentrations elicit, respectively, transient and sustained activation of TrkB receptor and its downstream signaling, leading to differential molecular and cellular functions. In cultured neurons, sustained TrkB activation promotes neuronal dendritic arborization and spinogenesis, whereas transient TrkB activation facilitates dendritic growth and spine morphogenesis. In hippocampal slices, slow delivery of BDNF facilitates LTP, whereas fast application of BDNF enhances basal synaptic transmission in schaffer collateral synapses. High-frequency stimulation of neurons converts BDNF-induced TrkB signaling from a transient to a sustained mode. These initial insights lay the foundation for future investigation of the BDNF-TrkB pathway, and analogous signaling pathways to gain a comprehensive understanding to enable translational research.


acute and chronic; neuronal activity; neurotrophin; signaling kinetics; transient and sustained

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