title: Loss of PSD-95 enrichment is not a prerequisite for spine retraction.
abstract: Changes in neuronal structure are thought to underlie long-term behavioral modifications associated with learning and memory. In particular, considerable evidence implicates the destabilization and retraction of dendritic spines along with the loss of spine synapses as an important cellular mechanism for refining brain circuits, yet the molecular mechanisms regulating spine elimination remain ill-defined. The postsynaptic density protein, PSD-95, is highly enriched in dendritic spines and has been associated with spine stability. Because spines with low levels of PSD-95 are more dynamic, and the recruitment of PSD-95 to nascent spines has been associated with spine stabilization, we hypothesized that loss of PSD-95 enrichment would be a prerequisite for spine retraction. To test this hypothesis, we used dual-color time-lapse two-photon microscopy to monitor rat hippocampal pyramidal neurons cotransfected with PSD-95-GFP and DsRed-Express, and we analyzed the relationship between PSD-95-GFP enrichment and spine morphological changes. Consistent with our hypothesis, we found that the majority of spines that retracted were relatively unenriched for PSD-95-GFP. However, in the subset of PSD-95-GFP-enriched spines that retracted, spine shrinkage and loss of PSD-95-GFP were tightly coupled, suggesting that loss of PSD-95-GFP enrichment did not precede spine retraction. Moreover, we found that, in some instances, spine retraction resulted in a significant enrichment of PSD-95-GFP on the dendritic shaft. Our data support a model of spine retraction in which loss of PSD-95 enrichment is not required prior to the destabilization of spines.
authors.affiliation: Center for Neuroscience, University of California, Davis, California 95618, USA.
authors.forename: Georgia F
authors.initials: GF
authors.lastname: Woods
authors.forename: Won Chan
authors.initials: WC
authors.lastname: Oh
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Boudewyn
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Mikula
authors.forename: Karen
authors.initials: K
authors.lastname: Zito
mesh_terms: D000818:Animals; D049229:Dendritic Spines / Q000235:genetics / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D047908:Intracellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics*; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000502:physiology* / Q000648:ultrastructure*; D020871:RNA Stability / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000235:genetics; D014162:Transfection / Q000379:methods
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins