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Updated: May 28, 2026
Real-time Imaging of Axonal Transport of Quantum Dot-labeled BDNF in Primary Neurons
Published on: September 15, 2014
BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions
Xindao Hu1, Lauren Ballo, Lauren Pietila
1Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
Abstract:
Microtubules (MTs) are capable of entering dendritic spines in mature hippocampal neurons through dynamic polymerization. Although these MT invasions are directly associated with neuronal activity, their function remains unknown. Here we demonstrate in mouse hippocampal neurons that MT entries into spines regulate the increase in postsynaptic density-95 (PSD-95) protein after brain-derived neurotrophic factor (BDNF) treatment. Using multiwavelength total internal reflectance fluorescence microscopy, we show that BDNF prolonged the average MT dwell time in spines and that this effect was dependent on TrkB receptor activation. Further examination revealed that peaks of MT polymerization into spines corresponded to rapid PSD-95 increases in the spine head. Over time, spines targeted by MTs after BDNF application, but not before, showed a robust increase in PSD-95. Conversely, spines completely devoid of MT invasions showed no significant change in the level of PSD-95. Pharmacological inhibition of MT dynamics abolished the BDNF-induced increase in PSD-95. Together, these results support the hypothesis that the well known increase in PSD-95 within spines after BDNF treatment is dependent on MT invasions of dendritic spines. Thus, our study provides a direct link between dynamic MTs and the postsynaptic structure, and provides a functional role for MT invasion of dendritic spines.
Insights
Microtubules (MTs) invade dendritic spines, a process regulated by brain-derived neurotrophic factor (BDNF). This invasion is crucial for increasing postsynaptic density-95 (PSD-95) protein levels in the synapse.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Microtubules (MTs) dynamically polymerize and enter dendritic spines in mature hippocampal neurons.
- While MT invasion correlates with neuronal activity, its functional significance remains unclear.
Purpose of the Study:
- To investigate the functional role of MT invasion into dendritic spines.
- To determine if MT invasion regulates postsynaptic protein levels, specifically postsynaptic density-95 (PSD-95), following BDNF treatment.
Main Methods:
- Utilized multiwavelength total internal reflectance fluorescence microscopy in mouse hippocampal neurons.
- Investigated the effects of BDNF treatment and TrkB receptor activation on MT dynamics within spines.
- Assessed PSD-95 protein levels in spines using microscopy and quantified changes in response to MT invasion and pharmacological interventions.
Main Results:
- BDNF treatment prolonged MT dwell time in spines, dependent on TrkB receptor activation.
- Peaks of MT polymerization into spines correlated with rapid increases in PSD-95.
- Spines invaded by MTs after BDNF application showed a significant increase in PSD-95, unlike spines without MT invasion.
- Inhibiting MT dynamics abolished BDNF-induced PSD-95 increases.
Conclusions:
- MT invasion of dendritic spines is essential for the BDNF-induced increase in PSD-95.
- This study establishes a direct functional link between dynamic MTs and postsynaptic structure regulation.
- Provides a functional role for MT invasion in synaptic plasticity and postsynaptic remodeling.
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