Faculty Opinions recommendation of Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity.

2007 ◽  
Author(s):  
Akihiro Kusumi
Keyword(s):  
Ampa Receptors ◽  
Synaptic Activity

scholarly journals AMPA receptors in the synapse turnover by monomer diffusion

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Jyoji Morise ◽  
Kenichi G. N. Suzuki ◽  
Ayaka Kitagawa ◽  
Yoshihiko Wakazono ◽  
Kogo Takamiya ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Synaptic Plasticity ◽  
Learning And Memory ◽  
Ampa Receptors ◽  
Single Molecules ◽  
Lateral Diffusion ◽  
Synaptic Function ◽  
Synaptic Activity ◽  
Monomer Diffusion

AbstractThe number and subunit compositions of AMPA receptors (AMPARs), hetero- or homotetramers composed of four subunits GluA1–4, in the synapse is carefully tuned to sustain basic synaptic activity. This enables stimulation-induced synaptic plasticity, which is central to learning and memory. The AMPAR tetramers have been widely believed to be stable from their formation in the endoplasmic reticulum until their proteolytic decomposition. However, by observing GluA1 and GluA2 at the level of single molecules, we find that the homo- and heterotetramers are metastable, instantaneously falling apart into monomers, dimers, or trimers (in 100 and 200 ms, respectively), which readily form tetramers again. In the dendritic plasma membrane, GluA1 and GluA2 monomers and dimers are far more mobile than tetramers and enter and exit from the synaptic regions. We conclude that AMPAR turnover by lateral diffusion, essential for sustaining synaptic function, is largely done by monomers of AMPAR subunits, rather than preformed tetramers.

scholarly journals Synaptic Activity-Dependent Changes in the Hippocampal Palmitoylome

2021 ◽  
Author(s):  
Glory Nasseri ◽  
Nusrat Matin ◽  
Kira Tosefsky ◽  
Richard Greg Stacey ◽  
Stephane Flibotte ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Ampa Receptors ◽  
Protein S ◽  
Postsynaptic Membrane ◽  
Synaptic Activity ◽  
Synaptic Proteins ◽  
Full Characterization ◽  
Metabolic Functions ◽  
Synapse Plasticity ◽  
Activity Dependent

Dynamic protein S-palmitoylation is critical for neuronal function, development, and synaptic plasticity. Activity-dependent changes in palmitoylation have been observed for several neuronal substrates, however a full characterization of the activity-regulated palmitoylome is lacking. Here, we use an unbiased approach to identify differentially palmitoylated proteins in the mouse hippocampus following context-dependent fear conditioning. Of the 121 differentially palmitoylated proteins identified 63 were synaptic proteins, while others were associated with metabolic functions, cytoskeletal organization, and signal transduction. The vast majority of synaptic proteins exhibited increased palmitoylation following fear conditioning, whereas proteins that exhibited decreased palmitoylation were predominantly associated with metabolic processes. We show a link between dynamic palmitoylation and synapse plasticity by demonstrating that the palmitoylation of one of our identified proteins, PRG-1/LPPR4, is essential for activity-induced insertion of AMPA receptors into the postsynaptic membrane. Together, this study identifies networks of synaptic proteins whose dynamic palmitoylation may play a central role in learning and memory.

scholarly journals MicroRNA-186-5p controls GluA2 surface expression and synaptic scaling in hippocampal neurons

2019 ◽  
Vol 116 (12) ◽  
pp. 5727-5736 ◽  
Author(s):  
Mariline M. Silva ◽  
Beatriz Rodrigues ◽  
Joana Fernandes ◽  
Sandra D. Santos ◽  
Laura Carreto ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Hippocampal Neurons ◽  
Surface Expression ◽  
Receptor Expression ◽  
Synaptic Activity ◽  
Synaptic Scaling ◽  
Posttranscriptional Control ◽  
Direct Target ◽  
Activity Dependent

Homeostatic synaptic scaling is a negative feedback response to fluctuations in synaptic strength induced by developmental or learning-related processes, which maintains neuronal activity stable. Although several components of the synaptic scaling apparatus have been characterized, the intrinsic regulatory mechanisms promoting scaling remain largely unknown. MicroRNAs may contribute to posttranscriptional control of mRNAs implicated in different stages of synaptic scaling, but their role in these mechanisms is still undervalued. Here, we report that chronic blockade of glutamate receptors of the AMPA and NMDA types in hippocampal neurons in culture induces changes in the neuronal mRNA and miRNA transcriptomes, leading to synaptic upscaling. Specifically, we show that synaptic activity blockade persistently down-regulates miR-186-5p. Moreover, we describe a conserved miR-186-5p-binding site within the 3′UTR of the mRNA encoding the AMPA receptor GluA2 subunit, and demonstrate that GluA2 is a direct target of miR-186-5p. Overexpression of miR-186 decreased GluA2 surface levels, increased synaptic expression of GluA2-lacking AMPA receptors, and blocked synaptic scaling, whereas inhibition of miR-186-5p increased GluA2 surface levels and the amplitude and frequency of AMPA receptor-mediated currents, and mimicked excitatory synaptic scaling induced by synaptic inactivity. Our findings elucidate an activity-dependent miRNA-mediated mechanism for regulation of AMPA receptor expression.

scholarly journals Leaky wiring of the brain: local cluster of coupled synapses and extracellular signal integration

2021 ◽  
Author(s):  
E.A. Matthews ◽  
W. Sun ◽  
S.M. McMahon ◽  
M. Doengi ◽  
L. Halka ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Extracellular Space ◽  
Synaptic Activity ◽  
Learning Performance ◽  
Local Cluster ◽  
Extracellular Signal ◽  
Vesicular Release ◽  
Neurotransmitter Glutamate ◽  
Point To Point ◽  
The Brain

AbstractThe wiring scheme is key to the function of the brain. Neurons are structurally wired by synapses and it is a long-held view that most synapses in the CNS are sufficiently isolated to avoid cross-talk to AMPA receptors of neighboring synapses. On the contrary, we show here with optical reporter proteins that the neurotransmitter glutamate regularly spreads far into the extracellular space (>1μm) after vesicular release. Together with 2P-glutamate uncaging our data suggest that multi-vesicular release rather regularly generates crosstalk responses at AMPA receptors of ~2-4 adjacent synapses (>70 synapses for NMDA receptors). Extracellular spread of glutamate is cooperative and coincident synaptic release events show enhanced spread and cause supra-additive activation of postsynapses. Thus, synaptic wiring of the brain seems to deviate more from point-to-point communication than previously reported and involves broadcasting information to very local neighborhoods which can stabilize learning performance and allow for integration of synaptic activity within the extracellular space.

scholarly journals Shisa6 traps AMPA receptors at postsynaptic sites and prevents their desensitization during synaptic activity

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Remco V. Klaassen ◽  
Jasper Stroeder ◽  
Françoise Coussen ◽  
Anne-Sophie Hafner ◽  
Jennifer D. Petersen ◽  
...  
Keyword(s):  
Ampa Receptors ◽  
Synaptic Activity

Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype

Nature ◽  
2000 ◽  
Vol 405 (6785) ◽  
pp. 454-458 ◽  
Author(s):  
Si-Qiong June Liu ◽  
Stuart G. Cull-Candy
Keyword(s):  
Ampa Receptors ◽  
Synaptic Activity ◽  
Receptor Subtype

scholarly journals Ocular hypertension drives remodeling of AMPA receptors in select populations of retinal ganglion cells

2019 ◽  
Author(s):  
Asia L. Sladek ◽  
Scott Nawy
Keyword(s):  
Retinal Ganglion Cells ◽  
Ampa Receptors ◽  
Ganglion Cells ◽  
Synaptic Activity ◽  
Retinal Ganglion ◽  
Degenerative Diseases ◽  
Aberrant Expression ◽  
Pathological Conditions ◽  
Cb1 Antagonist ◽  
Genomic Editing

AbstractAMPA receptors in the CNS are normally impermeable to Ca2+ but aberrant expression of Ca2+-permeable AMPA receptors (CP-AMPARs) occurs in pathological conditions such as ischemia or epilepsy, or in degenerative diseases such as ALS. Here we show that select populations of retinal ganglion cells (RGCs) similarly express high levels of CP-AMPARs in a mouse model of glaucoma. CP-AMPAR expression increased dramatically in both α On and α transient Off RGCs, and this increase was prevented by genomic editing of the GluA2 Q/R site. α On RGCs with elevated CP-AMPAR levels displayed profound synaptic depression, which was reduced by selectively blocking CP-AMPARs, buffering Ca2+ with BAPTA, or with the CB1 antagonist AM251, suggesting that depression was mediated by a retrograde transmitter which might be triggered by influx of Ca2+ through CP-AMPARs. Thus OHT alters the composition of AMPARs and modulates patterns of synaptic activity in select populations of RGCs.

scholarly journals Sorting nexin-27 regulates AMPA receptor trafficking through the synaptic adhesion protein LRFN2

2020 ◽  
Author(s):  
Kirsty J. McMillan ◽  
Paul J. Banks ◽  
Francesca L. N. Hellel ◽  
Ruth E. Carmichael ◽  
Thomas Clairfeuille ◽  
...  
Keyword(s):  
Ampa Receptor ◽  
Ampa Receptors ◽  
Long Term Potentiation ◽  
Surface Expression ◽  
Synaptic Activity ◽  
Endosomal Sorting ◽  
Sorting Nexin ◽  
Term Potentiation ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain

AbstractThe endosome-associated cargo adaptor sorting nexin-27 (SNX27) is linked to various neuropathologies through sorting of integral proteins to the synaptic surface, most notably AMPA receptors. To provide a broader view of SNX27-associated pathologies we have performed unbiased proteomics to identify new neuronal SNX27-dependent cargoes, and identified proteins linked to excitotoxicity (SLC1A3, SLC4A7, SLC6A11), epilepsy, intellectual disabilities and working memory deficits (KCNT2, ADAM22, KIDINS220, LRFN2). Focusing on the synaptic adhesion molecule leucine-rich repeat and fibronectin type-III domain-containing protein 2 (LRFN2), we establish that SNX27 binds to LRFN2 and is responsible for regulating its endosomal sorting. LRFN2 associates with AMPA receptors and knockdown of LRFN2 phenocopies SNX27 depletion in decreasing surface expression of AMPA receptors, reducing synaptic activity and attenuating hippocampal long-term potentiation. Our evidence suggests that, in contrast to previous reports, SNX27 does not directly bind to AMPA receptors, and instead controls AMPA receptor-mediated synaptic transmission and plasticity indirectly through the endosomal sorting of LRFN2. Overall, our study provides new molecular insight into the perturbed function of SNX27 and LRFN2 in a range of neurological conditions.

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