Rapid Redistribution of Synaptic PSD-95 in the Neocortex In Vivo

By Noah W. Gray, Robby M. Weimer, I. Bureau, Karel Svoboda. 2006

354 citations recorded by the source corpus.

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 τ r ~ 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 (τ r ~ 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.

Subfields: Cellular and Molecular Neuroscience, Cognitive Neuroscience

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Citations in the corpus

Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window (2009, neutral): “(4) Some spines can be absent in one of the imaging sessions, whereas present in all others.”
Imaging neural activity in worms, flies and mice with improved GCaMP calcium indicators (2009, methodology): “Genes encoding GCaMP variants, TN-XXL and D3cpV were subcloned into the pCAGGS vector with a CAG promoter (CMV enhancer, β-actin promoter and regulatory element from the woodchuck hepatitis viru”
COORDINATION OF SIZE AND NUMBER OF EXCITATORY AND INHIBITORY SYNAPSES RESULTS IN A BALANCED STRUCTURAL PLASTICITY ALONG MATURE HIPPOCAMPAL CA1 DENDRITES DURING LTP (2011, background): “Physiological recordings and functional imaging supports this hypothesis (Gray et al., 2006; Losonczy and Magee, 2006; Tsuriel et al., 2006; Harvey and Svoboda, 2007; De Roo et al., 2008; Harvey et al., 2008; Losonczy et al., 2008; Rose et al., 2009; Zhong et al., 2009).”
Heterosynaptic structural plasticity on local dendritic segments of hippocampal CA1 neurons (2014, background): “For example, key structural components of the synapse such as PSD-95, which has been associated with spine stability, could be redistributed by diffusion to growing synapses at the expense of their neighbors (Gray et al., 2006; Tsuriel et al., 2006).”
Do thin spines learn to be mushroom spines that remember? (2007, background): “Longer thinner spine necks transiently trap more molecules such as inositol 1,4,5triphosphate [28] and PSD95 [29], which further regulate Ca or synaptic efficacy.”
The Tol2kit: A multisite gateway‐based construction kit for Tol2 transposon transgenesis constructs (2007, methodology): “For middle entry clones, EGFP, EGFPCAAX, and nlsEGFP were amplified from the corresponding pCS2 clones; mCherry from pKR5-mCherry (Gray et al., 2006); and Gal4VP16 from a clone from R. Köster. mCherryCAAX and nlsmCherry were generated by adding the relevant localization sequences by PCR, and H2A.”
Locally dynamic synaptic learning rules in pyramidal neuron dendrites (2007, positive): “The timescale and spatial scale of crosstalk are consistent with a diffusing cytoplasmic factor 33,34 .”
Channelrhodopsin-2–assisted circuit mapping of long-range callosal projections (2007, methodology): “The constructs were inserted into pCAGGS vector modified for in utero electroporatio”