Role of AMPA Receptor Cycling in Synaptic Transmission and Plasticity

Lüscher, Christian; Xia, Houhui; Beattie, Eric C.; Carroll, Reed C.; Zastrow, Mark von; Malenka, Robert C.

doi:10.1016/s0896-6273(00)81119-8

Cited by 642 publications

(592 citation statements)

References 41 publications

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“…Most studied in this respect are the actions of CNS glutamatergic receptors that participate in numerous signal transduction and regulatory events. Prominent examples include forms of synaptic plasticity involving a rapid redistribution of AMPA receptors on the cell surface as well as transfer between surface and intracellular locations (Nishimune et al, 1998;Osten et al, 1998;Carroll et al, 1999;Luscher et al, 1999;Hayashi et al, 2000;Hanley et al, 2002). NMDA receptors undergo several other forms of calcium-controlled regulation including activity-dependent inactivation and rundown (Legendre et al, 1993;Westbrook, 1993a, 1993b;Westbrook et al, 1997;Wyszynski et al, 1997;Zhang et al, 1998;Krupp et al, 1999).…”

Section: Short-term Consequencesmentioning

confidence: 99%

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

2002

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Nicotinic receptors are cation-ion selective ligand-gated ion channels that are expressed throughout the nervous system. Most have significant calcium permeabilities, enabling them to regulate calcium-dependent events. One of the most abundant is a species composed of the ␣7 gene product and having a relative calcium permeability equivalent to that of NMDA receptors. The ␣7-containing receptors can be found presynaptically where they modulate transmitter release, and postsynaptically where they generate excitatory responses. They can also be found in perisynaptic locations where they modulate other inputs to the neuron and can activate a variety of downstream signaling pathways. The effects the receptors produce depend critically on the sites at which they are clustered. Instructive preparations for examining ␣7-containing receptors are the rat hippocampus, where they are thought to play a modulatory role, and the chick ciliary ganglion, where they participate in throughput transmission as well as regulatory signaling. Relatively high levels of ␣7-containing receptors are found in the two preparations, and the receptors display a variety of synaptic options and functions in the two cases. Progress is starting to be made in understanding the mechanisms responsible for localizing the receptors at specific sites and in identifying components tethered in the vicinity of the receptors that may facilitate signal transduction and downstream signaling.

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Section: Short-term Consequencesmentioning

confidence: 99%

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

2002

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“…Is there a population of AMPARs that under normal conditions are stably held at the synapse? One suggestion that such a stable population exists is that the rundown of AMPAR-mediated EPSC amplitude induced by inhibitors of exocytosis is incomplete 12 . Another suggestion of such a stable population is that the glutamate-induced removal of AMPARs from the surface is not accompanied by an increase in the rate of endocytosis 27 , suggesting that internalization is rate-limited by release of AMPARs from anchors at the synapse.…”

Section: When Do Ampars Take a Break?mentioning

confidence: 99%

“…have been loaded with toxins that cleave vSNARE proteins or dominant-negative peptides that disrupt dynamin function, thus blocking exo-or endocytosis in the postsynaptic cell 12 . When exocytosis was blocked, EPSC amplitudes decreased over a time period of 30 min.…”

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confidence: 99%

“…The available evidence suggests that the endocytotic arm of this recycling occurs via dynamindependent endocytosis of clathrin-coated vesicles 12 , whereas the exocytotic arm requires some of the players in vesicle fusion that have been described in transmitter release, including SNAP (Ref. 15 ), synaptobrevin 12 and N-ethylmaleimide-sensitive fusion protein (NSF) 12,[16][17][18] .…”

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confidence: 99%

“…15 ), synaptobrevin 12 and N-ethylmaleimide-sensitive fusion protein (NSF) 12,[16][17][18] . An intriguing, but poorly understood, aspect of exocytosis is that GluR2 has been shown to specifically interact with NSF (see Table 1), which is enriched in the postsynaptic density (PSD) (for reviews see Refs 19,20 ).…”

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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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Neural Analysis of Learning in Simple Systems

Krasne

2002

Stevens' Handbook of Experimental Psychology

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This chapter reviews work on several kinds of behavioral learning and neural analogs of learning that have been analyzed at the physiological level in recent years. The specific forms of behavioral learning discussed are habituation, sensitization, and classical conditioning in Aplysia, and classical conditioning of eyeblink responses in mammals. The form of synaptic plasticity known as long‐term potentiation, which provides a neural model of classical conditioning, is also discussed as is research concerned with the possible role of hippocampal long‐term potentiation in behavioral learning. Currently available data suggest that learning may be due to intrinsic changes in the efficacy of synaptic transmission due to altered transmitter release, altered responsiveness of neurons to released chemical transmitters, and morphological changes at synapses. These changes appear to be induced via intracellular chemical signalling systems with phosphorylation of biological active proteins such as receptors, channels, and enzymes playing important causative roles. Current information on mechanisms involved in stabilizing synaptic change (i.e., memory), including the likely involvement of new genetic transcription in establishment of long term memory, are discussed. Also considered are physiological insights into the conditions responsible for production of new learning, including discussion of the relationships between contiguity and effect and possible mechanisms of blocking.

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Role of AMPA Receptor Cycling in Synaptic Transmission and Plasticity

Cited by 642 publications

References 41 publications

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

Nicotinic α7 receptors: Synaptic options and downstream signaling in neurons

Restless AMPA receptors: implications for synaptic transmission and plasticity

Neural Analysis of Learning in Simple Systems

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