Autocrine BDNF-TrkB signalling within a single dendritic spine.

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are vital for neuronal plasticity and learning.
• The precise spatiotemporal dynamics of BDNF release and TrkB activation during structural long-term potentiation (sLTP) remain unclear.

Purpose of the Study:

• To investigate whether BDNF is released and TrkB is activated during sLTP.
• To determine the timing and location of BDNF release and TrkB activation.
• To elucidate the role of this signaling pathway in synaptic plasticity.

Main Methods:

• Utilized fluorescence resonance energy transfer (FRET)-based sensors and two-photon fluorescence lifetime imaging microscopy to monitor TrkB activity in single dendritic spines.
• Employed electron microscopy to localize endogenous BDNF.
• Used glutamate uncaging and BDNF fused to superecliptic pHluorin to track BDNF release.

Main Results:

• Observed rapid (onset < 1 min) and sustained (> 20 min) TrkB activation in stimulated spines post-sLTP induction.
• Demonstrated that TrkB activation depends on N-methyl-D-aspartate receptor (NMDAR) and CaMKII signaling, and on postsynaptically synthesized BDNF.
• Confirmed postsynaptic BDNF localization and showed time-locked BDNF release from single dendritic spines.

Conclusions:

• Established a spine-autonomous, autocrine signaling mechanism where NMDAR-CaMKII-dependent BDNF release from stimulated spines activates TrkB on the same spines.
• This BDNF-TrkB pathway is crucial for both structural and functional long-term potentiation (LTP).
• Provides new insights into the molecular mechanisms underlying learning and memory.