Relationship Between Synaptic AMPAR and Spine Dynamics: Impairments in the FXS Mouse

Overview

Journal Cereb Cortex

Publisher Oxford University Press

Specialty Neurology

Date 2017 May 26

PMID 28541473

Citations 25

Authors

Anand Suresh

Anna Dunaevsky

Affiliations

Soon will be listed here.

Abstract

Structural dynamics of dendritic spines are important for memory and learning and are impaired in neurodevelopmental disorders such as fragile X syndrome. Spine dynamics are regulated by activity-dependent mechanisms that involve modulation of AMPA receptors (AMPAR); however, the relationship between AMPAR and spine dynamics in vivo and how these are altered in FXS mouse model is not known. Here, we tracked AMPAR and spines over multiple days in vivo in the cortex and found that dendritic spines in the fmr1 KO mouse were denser, smaller, had higher turnover rates and contained less sGluA2 compared to littermate controls. Although, KO spines maintained the relationship between AMPAR and spine stability, AMPAR levels in the KO were more dynamic with larger proportion of spines showing multiple dynamic events of AMPAR. Directional changes in sGluA2 were also observed in newly formed and eliminated spines, with KO spines displaying greater loss of AMPAR before elimination. Thus, we demonstrate that AMPAR levels within spines not are only continuously dynamic, but are also predictive of spine behavior, with impairments observed in the fmr1 KO mice.

Citing Articles

Activity of human-specific Interlaminar Astrocytes in a Chimeric Mouse Model of Fragile X Syndrome.

Anding A, Ren B, Padmashri R, Burkovetskaya M, Dunaevsky A bioRxiv. 2025; .

PMID: 40060700 PMC: 11888414. DOI: 10.1101/2025.02.26.640426.

Translational modulator ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome.

Coulson R, Frattini V, Moyer C, Hodges J, Walter P, Mourrain P iScience. 2024; 27(4):109259.

PMID: 38510125 PMC: 10951902. DOI: 10.1016/j.isci.2024.109259.

Stimulus-dependent synaptic plasticity underlies neuronal circuitry refinement in the mouse primary visual cortex.

Lopez-Ortega E, Yoon Choi J, Hong I, Roth R, Cudmore R, Huganir R Cell Rep. 2024; 43(4):113966.

PMID: 38507408 PMC: 11210464. DOI: 10.1016/j.celrep.2024.113966.

EF1α-associated protein complexes affect dendritic spine plasticity by regulating microglial phagocytosis in Fmr1 knock-out mice.

Su P, Yan S, Chen K, Huang L, Wang L, Lee F Mol Psychiatry. 2024; 29(4):1099-1113.

PMID: 38212373 DOI: 10.1038/s41380-023-02396-2.

Impairments in endogenous AMPA receptor dynamics correlates with learning deficits in Alzheimer's disease model mice.

Lu K, Li C, Liu J, Wang J, Li Y, He B Proc Natl Acad Sci U S A. 2023; 120(40):e2303878120.

PMID: 37748061 PMC: 10556575. DOI: 10.1073/pnas.2303878120.

References

Pan F, Aldridge G, Greenough W, Gan W . Dendritic spine instability and insensitivity to modulation by sensory experience in a mouse model of fragile X syndrome. Proc Natl Acad Sci U S A. 2010; 107(41):17768-73. PMC: 2955121. DOI: 10.1073/pnas.1012496107. View

Malenka R, Bear M . LTP and LTD: an embarrassment of riches. Neuron. 2004; 44(1):5-21. DOI: 10.1016/j.neuron.2004.09.012. View

Bastrikova N, Gardner G, Reece J, Jeromin A, Dudek S . Synapse elimination accompanies functional plasticity in hippocampal neurons. Proc Natl Acad Sci U S A. 2008; 105(8):3123-7. PMC: 2268595. DOI: 10.1073/pnas.0800027105. View

Zhang Y, Cudmore R, Lin D, Linden D, Huganir R . Visualization of NMDA receptor-dependent AMPA receptor synaptic plasticity in vivo. Nat Neurosci. 2015; 18(3):402-7. PMC: 4339371. DOI: 10.1038/nn.3936. View

Fonseca R, Nagerl U, Bonhoeffer T . Neuronal activity determines the protein synthesis dependence of long-term potentiation. Nat Neurosci. 2006; 9(4):478-80. DOI: 10.1038/nn1667. View

Villa K, Berry K, Subramanian J, Cha J, Oh W, Kwon H . Inhibitory Synapses Are Repeatedly Assembled and Removed at Persistent Sites In Vivo. Neuron. 2016; 89(4):756-69. PMC: 4760889. DOI: 10.1016/j.neuron.2016.01.010. View

Kopec C, Real E, Kessels H, Malinow R . GluR1 links structural and functional plasticity at excitatory synapses. J Neurosci. 2007; 27(50):13706-18. PMC: 6673607. DOI: 10.1523/JNEUROSCI.3503-07.2007. View

Noguchi J, Nagaoka A, Watanabe S, Ellis-Davies G, Kitamura K, Kano M . In vivo two-photon uncaging of glutamate revealing the structure-function relationships of dendritic spines in the neocortex of adult mice. J Physiol. 2011; 589(Pt 10):2447-57. PMC: 3115818. DOI: 10.1113/jphysiol.2011.207100. View

Hinton V, Brown W, Wisniewski K, Rudelli R . Analysis of neocortex in three males with the fragile X syndrome. Am J Med Genet. 1991; 41(3):289-94. DOI: 10.1002/ajmg.1320410306. View

10.

Holtmaat A, Bonhoeffer T, Chow D, Chuckowree J, de Paola V, Hofer S . Long-term, high-resolution imaging in the mouse neocortex through a chronic cranial window. Nat Protoc. 2009; 4(8):1128-44. PMC: 3072839. DOI: 10.1038/nprot.2009.89. View

11.

Alvarez V, Sabatini B . Anatomical and physiological plasticity of dendritic spines. Annu Rev Neurosci. 2007; 30:79-97. DOI: 10.1146/annurev.neuro.30.051606.094222. View

12.

Pologruto T, Sabatini B, Svoboda K . ScanImage: flexible software for operating laser scanning microscopes. Biomed Eng Online. 2003; 2:13. PMC: 161784. DOI: 10.1186/1475-925X-2-13. View

13.

Gray E . Axo-somatic and axo-dendritic synapses of the cerebral cortex: an electron microscope study. J Anat. 1959; 93:420-33. PMC: 1244535. View

14.

Makino H, Malinow R . Compartmentalized versus global synaptic plasticity on dendrites controlled by experience. Neuron. 2011; 72(6):1001-11. PMC: 3310180. DOI: 10.1016/j.neuron.2011.09.036. View

15.

Zhou Q, Homma K, Poo M . Shrinkage of dendritic spines associated with long-term depression of hippocampal synapses. Neuron. 2004; 44(5):749-57. DOI: 10.1016/j.neuron.2004.11.011. View

16.

Nishiyama J, Yasuda R . Biochemical Computation for Spine Structural Plasticity. Neuron. 2015; 87(1):63-75. PMC: 4722820. DOI: 10.1016/j.neuron.2015.05.043. View

17.

Anggono V, Huganir R . Regulation of AMPA receptor trafficking and synaptic plasticity. Curr Opin Neurobiol. 2012; 22(3):461-9. PMC: 3392447. DOI: 10.1016/j.conb.2011.12.006. View

18.

He C, Portera-Cailliau C . The trouble with spines in fragile X syndrome: density, maturity and plasticity. Neuroscience. 2012; 251:120-8. PMC: 3422423. DOI: 10.1016/j.neuroscience.2012.03.049. View

19.

Dolen G, Osterweil E, Rao B, Smith G, Auerbach B, Chattarji S . Correction of fragile X syndrome in mice. Neuron. 2007; 56(6):955-62. PMC: 2199268. DOI: 10.1016/j.neuron.2007.12.001. View

20.

Cane M, Maco B, Knott G, Holtmaat A . The relationship between PSD-95 clustering and spine stability in vivo. J Neurosci. 2014; 34(6):2075-86. PMC: 6608529. DOI: 10.1523/JNEUROSCI.3353-13.2014. View