Rapid redistribution of synaptic PSD-95 in the neocortex in vivo

Gray, N. W., Weimer, R. M., Bureau, I., Svoboda, K. (November 2006) Rapid redistribution of synaptic PSD-95 in the neocortex in vivo. PLoS Biol, 4 (11). e370. ISSN 1545-7885 (Electronic)

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Abstract

Most excitatory synapses terminate on dendritic spines. Spines vary in size, and their volumes are proportional to the area of the postsynaptic density (PSD) and synaptic strength. PSD-95 is an abundant multi-domain postsynaptic scaffolding protein that clusters glutamate receptors and organizes the associated signaling complexes. PSD-95 is thought to determine the size and strength of synapses. Although spines and their synapses can persist for months in vivo, PSD-95 and other PSD proteins have shorter half-lives in vitro, on the order of hours. To probe the mechanisms underlying synapse stability, we measured the dynamics of synaptic PSD-95 clusters in vivo. Using two-photon microscopy, we imaged PSD-95 tagged with GFP in layer 2/3 dendrites in the developing (postnatal day 10-21) barrel cortex. A subset of PSD-95 clusters was stable for days. Using two-photon photoactivation of PSD-95 tagged with photoactivatable GFP (paGFP), we measured the time over which PSD-95 molecules were retained in individual spines. Synaptic PSD-95 turned over rapidly (median retention times tau(r) is approximately 22-63 min from P10-P21) and exchanged with PSD-95 in neighboring spines by diffusion. PSDs therefore share a dynamic pool of PSD-95. Large PSDs in large spines captured more diffusing PSD-95 and also retained PSD-95 longer than small PSDs. Changes in the sizes of individual PSDs over days were associated with concomitant changes in PSD-95 retention times. Furthermore, retention times increased with developmental age (tau(r) is approximately 100 min at postnatal day 70) and decreased dramatically following sensory deprivation. Our data suggest that individual PSDs compete for PSD-95 and that the kinetic interactions between PSD molecules and PSDs are tuned to regulate PSD size.

Item Type:	Paper
Subjects:	organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells > dendritic spines bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > green fluorescent protein organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse Investigative techniques and equipment > microscopy > flourescence microscopy > two-photon excitation microscopy
CSHL Authors:	Bureau, Ingrid Gray, Noah W. Svoboda, Karel Weimer, Robby M.
Communities:	CSHL labs > Svoboda lab
Depositing User:	CSHL Librarian
Date:	November 2006
Date Deposited:	14 Dec 2011 17:43
Last Modified:	13 Apr 2018 19:40
PMCID:	PMC1634879
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/22803

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