Tuning Synaptic Strength by Regulation of AMPA Glutamate Receptor Localization

Overview

Journal Bioessays

Publisher Wiley

Specialties Biology
Cell Biology
Molecular Biology

Date 2024 May 2

PMID 38693811

Authors

Imogen Stockwell

Jake F Watson

Ingo H Greger

Affiliations

Soon will be listed here.

Abstract

Long-term potentiation (LTP) of excitatory synapses is a leading model to explain the concept of information storage in the brain. Multiple mechanisms contribute to LTP, but central amongst them is an increased sensitivity of the postsynaptic membrane to neurotransmitter release. This sensitivity is predominantly determined by the abundance and localization of AMPA-type glutamate receptors (AMPARs). A combination of AMPAR structural data, super-resolution imaging of excitatory synapses, and an abundance of electrophysiological studies are providing an ever-clearer picture of how AMPARs are recruited and organized at synaptic junctions. Here, we review the latest insights into this process, and discuss how both cytoplasmic and extracellular receptor elements cooperate to tune the AMPAR response at the hippocampal CA1 synapse.

Citing Articles

Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP.

Fuchsberger T, Stockwell I, Woods M, Brzosko Z, Greger I, Paulsen O Elife. 2025; 13.

PMID: 40063079 PMC: 11893101. DOI: 10.7554/eLife.100822.

AMPA receptor diffusional trapping machinery as an early therapeutic target in neurodegenerative and neuropsychiatric disorders.

Choquet D, Opazo P, Zhang H Transl Neurodegener. 2025; 14(1):8.

PMID: 39934896 PMC: 11817889. DOI: 10.1186/s40035-025-00470-z.

The GluA1 cytoplasmic tail regulates intracellular AMPA receptor trafficking and synaptic transmission onto dentate gyrus GABAergic interneurons, gating response to novelty.

Leana-Sandoval G, Kolli A, Chinn C, Madrid A, Lo I, Sandoval M bioRxiv. 2024; .

PMID: 39677714 PMC: 11643017. DOI: 10.1101/2024.12.01.626277.

The VGCC auxiliary subunit α2δ1 is an extracellular GluA1 interactor and regulates LTP, spatial memory, and seizure susceptibility.

Leana-Sandoval G, Kolli A, Sandoval M, Saavedra E, Li K, Chen L bioRxiv. 2024; .

PMID: 39677598 PMC: 11642997. DOI: 10.1101/2024.12.02.626379.

Structure and Topography of AMPA Receptor Scaffolding Complexes Visualized by CryoET.

Held R, Liang J, Esquivies L, Khan Y, Wang C, Azubel M bioRxiv. 2024; .

PMID: 39464045 PMC: 11507944. DOI: 10.1101/2024.10.19.619226.

References

Diering G, Huganir R . The AMPA Receptor Code of Synaptic Plasticity. Neuron. 2018; 100(2):314-329. PMC: 6214363. DOI: 10.1016/j.neuron.2018.10.018. View

Plant K, Pelkey K, Bortolotto Z, Morita D, Terashima A, McBain C . Transient incorporation of native GluR2-lacking AMPA receptors during hippocampal long-term potentiation. Nat Neurosci. 2006; 9(5):602-4. DOI: 10.1038/nn1678. View

Hosokawa T, Liu P, Cai Q, Ferreira J, Levet F, Butler C . CaMKII activation persistently segregates postsynaptic proteins via liquid phase separation. Nat Neurosci. 2021; 24(6):777-785. DOI: 10.1038/s41593-021-00843-3. View

Baranovic J, Plested A . Auxiliary subunits keep AMPA receptors compact during activation and desensitization. Elife. 2018; 7. PMC: 6324883. DOI: 10.7554/eLife.40548. View

Nicoll R, Schulman H . Synaptic memory and CaMKII. Physiol Rev. 2023; 103(4):2877-2925. PMC: 10642921. DOI: 10.1152/physrev.00034.2022. View

Sia G, Beique J, Rumbaugh G, Cho R, Worley P, Huganir R . Interaction of the N-terminal domain of the AMPA receptor GluR4 subunit with the neuronal pentraxin NP1 mediates GluR4 synaptic recruitment. Neuron. 2007; 55(1):87-102. DOI: 10.1016/j.neuron.2007.06.020. View

Durr K, Chen L, Stein R, De Zorzi R, Folea I, Walz T . Structure and dynamics of AMPA receptor GluA2 in resting, pre-open, and desensitized states. Cell. 2014; 158(4):778-792. PMC: 4263325. DOI: 10.1016/j.cell.2014.07.023. View

Ehrlich I, Malinow R . Postsynaptic density 95 controls AMPA receptor incorporation during long-term potentiation and experience-driven synaptic plasticity. J Neurosci. 2004; 24(4):916-27. PMC: 6729816. DOI: 10.1523/JNEUROSCI.4733-03.2004. View

Herguedas B, Kohegyi B, Dohrke J, Watson J, Zhang D, Ho H . Mechanisms underlying TARP modulation of the GluA1/2-γ8 AMPA receptor. Nat Commun. 2022; 13(1):734. PMC: 8826358. DOI: 10.1038/s41467-022-28404-7. View

10.

Chang M, Park J, Pelkey K, Grabenstatter H, Xu D, Linden D . Narp regulates homeostatic scaling of excitatory synapses on parvalbumin-expressing interneurons. Nat Neurosci. 2010; 13(9):1090-7. PMC: 2949072. DOI: 10.1038/nn.2621. View

11.

Purkey A, DellAcqua M . Phosphorylation-Dependent Regulation of Ca-Permeable AMPA Receptors During Hippocampal Synaptic Plasticity. Front Synaptic Neurosci. 2020; 12:8. PMC: 7119613. DOI: 10.3389/fnsyn.2020.00008. View

12.

Tarusawa E, Matsui K, Budisantoso T, Molnar E, Watanabe M, Matsui M . Input-specific intrasynaptic arrangements of ionotropic glutamate receptors and their impact on postsynaptic responses. J Neurosci. 2009; 29(41):12896-908. PMC: 6665298. DOI: 10.1523/JNEUROSCI.6160-08.2009. View

13.

Raghavachari S, Lisman J . Properties of quantal transmission at CA1 synapses. J Neurophysiol. 2004; 92(4):2456-67. DOI: 10.1152/jn.00258.2004. View

14.

Shi Y, Lu W, Milstein A, Nicoll R . The stoichiometry of AMPA receptors and TARPs varies by neuronal cell type. Neuron. 2009; 62(5):633-40. PMC: 3119531. DOI: 10.1016/j.neuron.2009.05.016. View

15.

Shi S, Hayashi Y, Esteban J, Malinow R . Subunit-specific rules governing AMPA receptor trafficking to synapses in hippocampal pyramidal neurons. Cell. 2001; 105(3):331-43. DOI: 10.1016/s0092-8674(01)00321-x. View

16.

Jia Z, Agopyan N, Miu P, Xiong Z, Henderson J, Gerlai R . Enhanced LTP in mice deficient in the AMPA receptor GluR2. Neuron. 1996; 17(5):945-56. DOI: 10.1016/s0896-6273(00)80225-1. View

17.

Groc L, Choquet D . Linking glutamate receptor movements and synapse function. Science. 2020; 368(6496). DOI: 10.1126/science.aay4631. View

18.

Nicoll R . A Brief History of Long-Term Potentiation. Neuron. 2017; 93(2):281-290. DOI: 10.1016/j.neuron.2016.12.015. View

19.

Sumioka A, Yan D, Tomita S . TARP phosphorylation regulates synaptic AMPA receptors through lipid bilayers. Neuron. 2010; 66(5):755-67. PMC: 2887694. DOI: 10.1016/j.neuron.2010.04.035. View

20.

Meyerson J, Kumar J, Chittori S, Rao P, Pierson J, Bartesaghi A . Structural mechanism of glutamate receptor activation and desensitization. Nature. 2014; 514(7522):328-34. PMC: 4199900. DOI: 10.1038/nature13603. View