BDNF-induced increase of PSD-95 in dendritic spines requires dynamic microtubule invasions.
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.
Neuroscience Training Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
Xindao
X
Hu
Lauren
L
Ballo
Lauren
L
Pietila
Chris
C
Viesselmann
Jason
J
Ballweg
Derek
D
Lumbard
Matt
M
Stevenson
Elliott
E
Merriam
Erik W
EW
Dent
D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D049229:Dendritic Spines / Q000187:drug effects* / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D009474:Neurons / Q000166:cytology*; D017711:Nonlinear Dynamics; D021381:Protein Transport / Q000187:drug effects; D013997:Time Factors; D014162:Transfection; D014404:Tubulin / Q000378:metabolism
D000199:Actins; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D008164:Luminescent Proteins; D008565:Membrane Proteins; D014404:Tubulin; C413663:fluorescent protein 583; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases