Rapid Spine Delivery and Redistribution of AMPA Receptors After Synaptic NMDA Receptor Activation

Shi, Song-Hai; Hayashi, Yasunori; Petralia, Ronald S.; Zaman, Shahid; Wenthold, Robert J.; Svoboda, Karel; Malinow, Roberto

doi:10.1126/science.284.5421.1811

Cited by 1,173 publications

(858 citation statements)

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“…Previous studies found no detectable changes in the VTA in total cellular protein levels of GluR1 between cocaine-and saline-treated mice (Ungless et al, 2001). However, because hippocampal LTP is dependent on the insertion of GluR1 into the postsynaptic membrane at synapses (Shi et al, 1999) rather than a simple increase in total cellular GluR1 levels, we reasoned that increases in AMPA receptor number at the surface might not be reflected in total cellular protein levels but only in surface receptor expression. Therefore, we examined surface expression of AMPA and NMDA receptors on VTA neurons from rats that had received a single dose of either saline or amphetamine 24 h earlier.…”

Section: Resultsmentioning

confidence: 77%

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Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.

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Section: Resultsmentioning

confidence: 77%

“…In the hippocampus, LTP is dependent on increased insertion of the AMPA receptor subunit, GluR1 (Shi et al, 1999;Zamanillo et al, 1999). Previous studies found no detectable changes in the VTA in total cellular protein levels of GluR1 between cocaine-and saline-treated mice (Ungless et al, 2001).…”

Section: Resultsmentioning

confidence: 95%

Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection

Faleiro

Jones

Kauer

2004

Neuropsychopharmacol

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“…Both results were blocked by NMDAR antagonists and postsynaptically applied tetanus toxin. In organotypic slice cultures overexpressing GluR1, activation of NMDARs was sufficient to translocate this subunit into spines 30 and drive the synaptic insertion of AMPARs made exclusively of GluR1 subunits. It was found that perfusion of neurons with activated Ca 2+ -calmodulin kinase type II (CaMKII) was sufficient to drive receptor insertion.…”

Section: Insertion Of Amparsmentioning

confidence: 99%

“…46 ) incorporated into postsynaptic membrane organelles, it was shown that high-frequency stimulation similar to the kind used to induce LTP led to Ca 2+ -dependent exocytosis. Evidence that this postsynaptic exocytosis delivers AMPARs comes from experiments in which transfection of CA1 neurons in organotypic slice cultures with a green fluorescent protein (GFP)-GluR1 fusion protein and application of an LTP induction protocol triggers the translocation of this protein from dendritic shafts to the spines 30 . Using rectification as an electrophysiological tag, the authors could show that GluR1 homomeric receptors were indeed synaptically inserted 47 .…”

Section: Do Ampars Move During Synaptic Plasticity? Ltpmentioning

confidence: 99%

Restless AMPA receptors: implications for synaptic transmission and plasticity

Lüscher

Frerking

2001

Trends in Neurosciences

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A central assumption in neurobiology holds that changes in the strength of individual synapses underlie changes in behavior. This concept is widely accepted in the case of learning and memory where LTP and LTD are the most compelling cellular models. It is therefore of great interest to understand, on a molecular level, how the brain regulates the strength of neuronal connections. We review a large body of evidence in support of the very straightforward regulation of synaptic strength by changing the number of postsynaptic receptors, and discuss the molecular machinery required for insertion and removal of AMPA receptors.The hypothesis that insertion of AMPA receptors (AMPARs) underlies the increase of synaptic strength associated with LTP was put forward almost 20 years ago 1 , but was largely ignored until the mid-1990s, resurfacing with quantal analysis of LTP (Ref. 2 ). However, only recently has it become the subject of direct experimental scrutiny.The spark for the myriad of research published in the past few years in the field was experiments conducted independently by two groups 3,4 , in which single connections between CA3 axons and CA1 pyramidal cells in acute hippocampal slices were functionally isolated and in some cases yielded only responses from NMDA receptors (NMDARs) and not AMPARs. Inducing LTP, however, caused the appearance of AMPAR mediated excitatory postsynaptic currents (EPSCs). This led to the proposal that a fraction of 'silent' synapses contain only NMDARs, and thus are functionally inactive at normal resting potential, but maintain the capability to undergo LTP, which would be expressed by AMPAR insertion. Although alternative explanations for these results have been proposed 5,6 , synapses with NMDARs but not AMPARs have now been directly identified anatomically in cultured hippocampal neurons using immunofluorescence 7,8 and with immuno-gold preparations visualized by electron microscopy in hippocampal slices 9-11 .AMPARs move from the cytoplasm to the surface and back again Constitutive recyclingIf LTP expression is caused by postsynaptic AMPAR insertion, it must be the case that AMPARs can be inserted into and removed from the postsynaptic membrane on a relatively rapid time scale. To test this experimentally, CA1 pyramidal cells in acute hippocampal slices * Christian.Luscher@medecine.unige.ch.

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“…8,9 However, the highest efficiency reported so far is 13.5%, 8 far less than other methods such as viral infection, which often reaches more than 40% of transduction efficiency. 10,11 To increase the transfection rate while maintaining low toxicity is the ultimate goal for every gene transfer method. The low efficiency of Ca 2+ -phosphate transfection has significantly limited its applications, such as in biochemical and electrophysiological analyses of gene functions.…”

Section: Introductionmentioning

confidence: 99%