Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity

Zhu, Jie; Esteban, José A.; Hayashi, Yasunori; Malinow, Roberto

doi:10.1038/80614

Cited by 385 publications

(422 citation statements)

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“…Interestingly, specific factors secreted from astrocytes directly affect the subunit composition and surface expression of synaptic AMPARs during development (for review see 69 ). It has also been reported that, early in development, GluA4 homomers are preferentially inserted into silent synapses at P5-7 in an activity-and NMDARdependent, but CaMKII-independent manner 12 . These GluA4 homomers are subsequently exchanged for GluA2-containing receptors by a constitutive process that maintains synaptic strength.…”

Section: Subunit Expression During Developmentmentioning

confidence: 90%

“…However, other studies of subunit abundance in rat hippocampus and cortex suggest AMPARs comprise mainly heteromers containing GluA1 and GluA2 or GluA2 and GluA3 [8][9][10] with approximately equivalent amounts of each heteromer complex 11 . GluA4, on the other hand is tightly developmentally regulated and is sparsely expressed at glutamatergic synapses in principal neurons in adult brain 12 . It should be noted, however, that GluA4 is a key determinant of the properties of AMPAR-mediated transmission in interneurons, especially in parvalbumin-containing inhibitory interneurons 13,14 .…”

Section: Subunit-specific Traffickingmentioning

confidence: 99%

“…These GluA4 homomers are subsequently exchanged for GluA2-containing receptors by a constitutive process that maintains synaptic strength. Thus, GluA4 trafficking underpins GluA1-independent developmental LTP and provides the mechanism for delivering AMPARs to previously silent synapses 12 . Furthermore, there is another shift in the composition of AMPARs by P21, as GluA3 levels increase and GluA1 levels decline.…”

Section: Subunit Expression During Developmentmentioning

confidence: 99%

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Synaptic AMPA receptor composition in development, plasticity and disease

2016

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. PrefaceAMPARs are assemblies of four core subunits, GluA1-4, that mediate most fast excitatory neurotransmission. The component subunits determine the functional properties of AMPARs and the prevailing view is that the subunit composition also determines AMPAR trafficking, which is dynamically regulated during development, synaptic plasticity, and in response to neuronal stress in disease. Recently, the subunit-dependence of AMPAR trafficking has been questioned leading to a reappraisal of the field. Here we review what is known, uncertain, conjectured and unknown about the roles of individual subunits and how they impact on AMPAR assembly, trafficking and function under normal and pathological conditions. IntroductionAMPA receptors (AMPARs) are a subtype of ionotropic glutamate receptors that are the 'work-horses' of fast excitatory neurotransmission in the CNS. Developmentallyand activity-regulated changes in the numbers and properties of AMPARs localized at the postsynaptic membrane are essential for excitatory synapse formation, stabilization, synaptic plasticity and neural circuit formation. Consequently, the logistics of the delivery, retention and removal of individual AMPARs with defined subunit compositions at specific synapses is highly complex. A typical cortical or hippocampal pyramidal neuron contains on the order of 10,000 synapses and the AMPARs at each synapse are independently and dynamically regulated in response to developmental cues, synaptic activity and environmental stresses. Furthermore, defects in the processes that control AMPAR assembly, trafficking and synaptic expression are intimately linked to psychiatric and neurological conditions, and also with cognitive decline in neurodegenerative diseases. Remarkable progress has been achieved in understanding how AMPAR trafficking, is orchestrated by a large array of AMPAR interacting proteins. These studies have established a set of hierarchical subunit-specific rules that control AMPAR trafficking under basal and activity-dependent conditions. Furthermore, there has been a growing appreciation that subunit composition can tune the properties of AMPARs to specific conditions. Nonetheless, how AMPARs comprising different subunits are differentially trafficked to control synaptic development, stabilisation and plasticity is a key unanswered question. Here, we provide an overview of the current state of knowledge of subunit-specific AMPAR trafficking and outline what we believe to be the key unresolved questions in the field. 2 Subunit-specific traffickingMost AMPARs are heterotetrameric assemblies of combinations of the subunits GluA1, GluA2, GluA3 and GluA4. AMPARs are expressed in both neurons and glia throughout the CNS 1 and have a turnover time of between 10 hours and 2 days depending on the type of neuron and developmental stage 2,3 . Each subunit has an identical membrane topology and c...

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Section: Subunit Expression During Developmentmentioning

confidence: 90%

Section: Subunit-specific Traffickingmentioning

confidence: 99%

Section: Subunit Expression During Developmentmentioning

confidence: 99%

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Synaptic AMPA receptor composition in development, plasticity and disease

2016

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“…GluA4-containing AMPAR can also be delivered into the synapse after neuronal conditioning (eg, Mokin and Keifer, 2004) and activity (eg, Zhu et al, 2000). In vitro model of eyeblink classical conditioning, where a weak electrical stimulation of the auditory nerve (the 'tone' CS) is paired with a strong stimulation of the trigeminal nerve (the 'air puff' US), leads to marked increased synaptic delivery of GluA4-containing AMPAR when compared with nonassociative stimulation (random presentations of CS and US) (eg, Mokin and Keifer, 2004).…”

Section: Discussionmentioning

confidence: 99%

The Membrane Proximal Region of AMPA Receptors in Lateral Amygdala is Essential for Fear Memory Formation

Ganea

Dines

Basu

et al. 2015

Neuropsychopharmacol

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The membrane proximal region (MPR) of AMPA receptor (AMPAR) is needed for receptor trafficking and synaptic plasticity. However, its roles in long-term memory formation are not known. To assess the possible roles of AMPAR-MPR in rat lateral amygdala (LA) in shortand long-term fear memory formation, we used glutamate receptors (GluAs)-MPR competitive peptides MPR(DD) and MPR(AA). The MPR(DD) peptide is derived from GluA1 MPR and was previously shown to impair synaptic plasticity and to inhibit GluA1 containing AMPAR insertion into the synapse in an activity-dependent manner. The MPR(AA) peptide is derived from GluA2/4 MPR, and this receptor fragment was shown to be essential for GluA4 protein interaction needed for its insertion into the neuronal membrane and synapse. The peptides were linked to a TAT peptide (TAT-MPR(DD) and TAT-MPR(AA)) to facilitate internalization into LA cells. Infusion of the TAT-MPR(DD) peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. Injection of TAT-MPR(DD) peptide into LA 30 min before fear conditioning impaired short-term fear memory formation. The TAT-MPR(DD) peptide had no effect on memory retrieval when injected into LA 30 min before fear memory test. Infusion of the TAT-MPR(AA) peptide into LA 30 min before fear conditioning led to a significant impairment of long-term fear memory formation. In contrast, the TAT-MPR(AA) had no effect on short-term fear memory formation. A TAT-control peptide had no effect on short-or longterm fear memory. These results show that the AMPAR-MPR in LA is needed for fear memory formation and that the MPR region of GluA1 is essential for acquisition of memory, whereas the MPR region of GluA4 is essential for long-term fear memory consolidation.

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“…Overexpression of different AMPAR subunits in CA1 neurons of organotypic hippocampal slice cultures indicates that receptors made of different subunits participate preferentially in various forms of AMPAR insertion. Although GluR2-and GluR3-containing receptors make up the bulk of constitutively recycling AMPARs, GluR1 dominates if receptors are inserted after appropriate NMDAR activation 32,33 . It is interesting to note that subunit-specificity of these interactions might vary from synapse to synapse.…”

Section: Insertion Of Amparsmentioning

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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Postnatal synaptic potentiation: Delivery of GluR4-containing AMPA receptors by spontaneous activity

Abstract: El artículo seleccionado no se encuentra disponible por ahora a texto completo por no haber sido facilitado todavía por el investigador a cargo del archivo del mismo.

Cited by 385 publications

References 43 publications

Synaptic AMPA receptor composition in development, plasticity and disease

Synaptic AMPA receptor composition in development, plasticity and disease

The Membrane Proximal Region of AMPA Receptors in Lateral Amygdala is Essential for Fear Memory Formation

Restless AMPA receptors: implications for synaptic transmission and plasticity

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