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Mechanisms and Functions of Activity-Regulated Cytoskeleton-Associated Protein in Synaptic Plasticity

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Abstract

Activity-regulated cytoskeleton-associated protein (Arc) is one of the most important regulators of cognitive functions in the brain regions. As a hub protein, Arc plays different roles in modulating synaptic plasticity. Arc supports the maintenance of long-term potentiation (LTP) by regulating actin cytoskeletal dynamics, while it guides the endocytosis of AMPAR in long-term depression (LTD). Moreover, Arc can self-assemble into capsids, leading to a new way of communicating among neurons. The transcription and translation of the immediate early gene Arc are rigorous procedures guided by numerous factors, and RNA polymerase II (Pol II) is considered to regulate the precise timing dynamics of gene expression. Since astrocytes can secrete brain-derived neurotrophic factor (BDNF) and L-lactate, their unique roles in Arc expression are emphasized. Here, we review the entire process of Arc expression and summarize the factors that can affect Arc expression and function, including noncoding RNAs, transcription factors, and posttranscriptional regulations. We also attempt to review the functional states and mechanisms of Arc in modulating synaptic plasticity. Furthermore, we discuss the recent progress in understanding the roles of Arc in the occurrence of major neurological disorders and provide new thoughts for future research on Arc.

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References

  1. Lyford GL, Yamagata K, Kaufmann WE et al (1995) Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron 14:433–445. https://doi.org/10.1016/0896-6273(95)90299-6

    Article  CAS  PubMed  Google Scholar 

  2. Link W, Konietzko U, Kauselmann G et al (1995) Somatodendritic expression of an immediate early gene is regulated by synaptic activity. Proc Natl Acad Sci USA 92:5734–5738. https://doi.org/10.1073/pnas.92.12.5734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kruijssen DLH, Wierenga CJ (2019) Single synapse LTP: a matter of context? Front Cell Neurosci 13:496. https://doi.org/10.3389/fncel.2019.00496

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Yu S, Wang G, Yao B et al (2022) Arc and Homer1 are involved in comorbid epilepsy and depression: a microarray data analysis. Epilepsy Behav EB 132:108738. https://doi.org/10.1016/j.yebeh.2022.108738

    Article  Google Scholar 

  5. Fernández-García S, Sancho-Balsells A, Longueville S et al (2020) Astrocytic BDNF and TrkB regulate severity and neuronal activity in mouse models of temporal lobe epilepsy. Cell Death Dis 11:411. https://doi.org/10.1038/s41419-020-2615-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Walczyk-Mooradally A, Holborn J et al (2021) Phosphorylation-dependent control of Activity-regulated cytoskeleton-associated protein (Arc) protein by TNIK. J Neurochem 158(5):1058–1073. https://doi.org/10.1111/jnc.15440

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Jr W, Jp A, Km H (2018) Roles for Arc in metabotropic glutamate receptor-dependent LTD and synapse elimination: implications in health and disease. Semin Cell Dev Biol 77. https://doi.org/10.1016/j.semcdb.2017.09.035

  8. Pevzner A, Miyashita T, Schiffman AJ, Guzowski JF (2012) Temporal dynamics of Arc gene induction in hippocampus: relationship to context memory formation. Neurobiol Learn Mem 97:313–320. https://doi.org/10.1016/j.nlm.2012.02.004

    Article  CAS  PubMed  Google Scholar 

  9. Saunders A, Core LJ, Lis JT (2006) Breaking barriers to transcription elongation. Nat Rev. Mol Cell Biol 7(8):557–567. https://doi.org/10.1038/nrm1981

    Article  CAS  PubMed  Google Scholar 

  10. Saha RN, Wissink EM, Bailey ER et al (2011) Rapid activity-induced transcription of Arc and other IEGs relies on poised RNA polymerase II. Nat Neurosci 14:848–856. https://doi.org/10.1038/nn.2839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Wu JQ, Snyder M (2008) RNA polymerase II stalling: loading at the start prepares genes for a sprint. Genome Biol 9(5):220. https://doi.org/10.1186/gb-2008-9-5-220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Narita T, Yamaguchi Y et al (2003) Human transcription elongation factor NELF: identification of novel subunits and reconstitution of the functionally active complex. Mol Cell Biol 23(6):1863–1873. https://doi.org/10.1128/MCB.23.6.1863-1873.2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Hedde PN, Malacrida L, Barylko B et al (2021) Membrane remodeling by Arc/Arg3.1. Front Mol Biosci 8:630625. https://doi.org/10.3389/fmolb.2021.630625

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kanai Y, Dohmae N, Hirokawa N (2004) Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 43:513–525. https://doi.org/10.1016/j.neuron.2004.07.022

    Article  CAS  PubMed  Google Scholar 

  15. Leal G, Comprido D, Duarte CB (2014) BDNF-induced local protein synthesis and synaptic plasticity. Neuropharmacology 76(Pt C):639–656. https://doi.org/10.1016/j.neuropharm.2013.04.005

    Article  CAS  PubMed  Google Scholar 

  16. Giorgi C, Moore MJ (2007) The nuclear nurture and cytoplasmic nature of localized mRNPs. Semin Cell Dev Biol 18:186–193. https://doi.org/10.1016/j.semcdb.2007.01.002

    Article  CAS  PubMed  Google Scholar 

  17. Huang F, Chotiner JK, Steward O (2007) Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites. J Neurosci Off J Soc Neurosci 27:9054–9067. https://doi.org/10.1523/JNEUROSCI.2410-07.2007

    Article  CAS  Google Scholar 

  18. Carmichael RE, Henley JM (2018) Transcriptional and post-translational regulation of Arc in synaptic plasticity. Semin Cell Dev Biol 77:3–9. https://doi.org/10.1016/j.semcdb.2017.09.007

    Article  CAS  PubMed  Google Scholar 

  19. Okuno H, Minatohara K, Bito H (2018) Inverse synaptic tagging: an inactive synapse-specific mechanism to capture activity-induced Arc/arg3.1 and to locally regulate spatial distribution of synaptic weights. Semin Cell Dev Biol 77:43–50. https://doi.org/10.1016/j.semcdb.2017.09.025

    Article  CAS  PubMed  Google Scholar 

  20. Nonaka M, Fujii H, Kim R et al (2014) Untangling the two-way signalling route from synapses to the nucleus, and from the nucleus back to the synapses. Philos Trans R Soc Lond B Biol Sci 369:20130150. https://doi.org/10.1098/rstb.2013.0150

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kyzar EJ, Zhang H, Pandey SC (2019) Adolescent alcohol exposure epigenetically suppresses amygdala Arc enhancer RNA expression to confer adult anxiety susceptibility. Biol Psychiatry 85:904–914. https://doi.org/10.1016/j.biopsych.2018.12.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Na Y, Park S, Lee C et al (2016) Real-time imaging reveals properties of glutamate-induced Arc/Arg 3.1 translation in neuronal dendrites. Neuron 91:561–573. https://doi.org/10.1016/j.neuron.2016.06.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fernández E, Collins MO et al (2017) Arc requires PSD95 for assembly into postsynaptic complexes involved with neural dysfunction and intelligence. Cell Rep 21(3):679–691. https://doi.org/10.1016/j.celrep.2017.09.045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Chen X, Jia B, Araki Y et al (2022) Arc weakens synapses by dispersing AMPA receptors from postsynaptic density via modulating PSD phase separation. Cell Res 32:914–930. https://doi.org/10.1038/s41422-022-00697-9

    Article  CAS  PubMed  Google Scholar 

  25. Ma K, Ding X, Song Q et al (2020) Lactate enhances Arc/arg3.1 expression through hydroxycarboxylic acid receptor 1-β-arrestin2 pathway in astrocytes. Neuropharmacology 171:108084. https://doi.org/10.1016/j.neuropharm.2020.108084

    Article  CAS  PubMed  Google Scholar 

  26. Messaoudi E, Kanhema T, Soulé J et al (2007) Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo. J Neurosci Off J Soc Neurosci 27:10445–10455. https://doi.org/10.1523/JNEUROSCI.2883-07.2007

    Article  CAS  Google Scholar 

  27. Bourne JN, Harris KM (2008) Balancing structure and function at hippocampal dendritic spines. Annu Rev Neurosci 31:47–67. https://doi.org/10.1146/annurev.neuro.31.060407.125646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Matsuzaki M, Honkura N, Ellis-Davies GCR, Kasai H (2004) Structural basis of long-term potentiation in single dendritic spines. Nature 429:761–766. https://doi.org/10.1038/nature02617

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zhang H, Bramham CR (2021) Arc/Arg3.1 function in long-term synaptic plasticity: emerging mechanisms and unresolved issues. Eur J Neurosci 54:6696–6712. https://doi.org/10.1111/ejn.14958

    Article  CAS  PubMed  Google Scholar 

  30. Kyrke-Smith M, Volk LJ, Cooke SF et al (2021) The immediate early gene Arc is not required for hippocampal long-term potentiation. J Neurosci Off J Soc Neurosci 41:4202–4211. https://doi.org/10.1523/JNEUROSCI.0008-20.2021

    Article  CAS  Google Scholar 

  31. Smith-Hicks C, Xiao B, Deng R et al (2010) SRF binding to SRE 6.9 in the Arc promoter is essential for LTD in cultured Purkinje cells. Nat Neurosci 13:1082–1089. https://doi.org/10.1038/nn.2611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Plath N, Ohana O, Dammermann B et al (2006) Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron 52:437–444. https://doi.org/10.1016/j.neuron.2006.08.024

    Article  CAS  PubMed  Google Scholar 

  33. Kedrov AV, Durymanov M, Anokhin KV (2019) The Arc gene: retroviral heritage in cognitive functions. Neuroscience Biobehav Rev 99:275–281. https://doi.org/10.1016/j.neubiorev.2019.02.006

    Article  CAS  Google Scholar 

  34. Nielsen LD, Pedersen CP, Erlendsson S (1993) Teilum K (2019) The capsid domain of Arc changes its Oligomerization propensity through direct interaction with the NMDA receptor. Struct Lond Engl 27:1071–1081.e5. https://doi.org/10.1016/j.str.2019.04.001

    Article  CAS  Google Scholar 

  35. Eriksen MS, Bramham CR (2022) Molecular physiology of Arc/Arg3.1: the oligomeric state hypothesis of synaptic plasticity. Acta Physiol Oxf Engl 236:e13886. https://doi.org/10.1111/apha.13886

    Article  CAS  Google Scholar 

  36. Pastuzyn ED, Day CE, Kearns RB et al (2018) The neuronal gene arc encodes a repurposed retrotransposon gag protein that mediates intercellular RNA transfer. Cell 172:275–288.e18. https://doi.org/10.1016/j.cell.2017.12.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Freed EO (2015) HIV-1 assembly, release and maturation. Nat Rev. Microbiol 13(8):484–496. https://doi.org/10.1038/nrmicro3490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang W, Wu J, Ward MD et al (2015) Structural basis of arc binding to synaptic proteins: implications for cognitive disease. Neuron 86:490–500. https://doi.org/10.1016/j.neuron.2015.03.030

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Myrum C, Soulé J, Bittins M et al (2017) Arc interacts with the integral endoplasmic reticulum protein, calnexin. Front Cell Neurosci 11:294. https://doi.org/10.3389/fncel.2017.00294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Peebles CL, Yoo J, Thwin MT et al (2010) Arc regulates spine morphology and maintains network stability in vivo. Proc Natl Acad Sci USA 107:18173–18178. https://doi.org/10.1073/pnas.1006546107

    Article  PubMed  PubMed Central  Google Scholar 

  41. Newpher TM, Harris S, Pringle J et al (2018) Regulation of spine structural plasticity by Arc/Arg3.1. Semin Cell Dev Biol 77:25–32. https://doi.org/10.1016/j.semcdb.2017.09.022

    Article  CAS  PubMed  Google Scholar 

  42. Nair RR, Patil S, Tiron A et al (2017) Dynamic Arc SUMOylation and selective interaction with F-actin-binding protein drebrin A in LTP consolidation in vivo. Front Synaptic Neurosci 9:8. https://doi.org/10.3389/fnsyn.2017.00008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Meng Y, Zhang Y, Tregoubov V et al (2002) Abnormal spine morphology and enhanced LTP in LIMK-1 knockout mice. Neuron 35:121–133. https://doi.org/10.1016/s0896-6273(02)00758-4

    Article  CAS  PubMed  Google Scholar 

  44. Trent S, Barnes P, Hall J, Thomas KL (2017) AMPA receptors control fear extinction through an Arc-dependent mechanism. Learn Mem Cold Spring Harb N 24:375–380. https://doi.org/10.1101/lm.045013.117

    Article  CAS  Google Scholar 

  45. Rial Verde EM, Lee-Osbourne J, Worley PF et al (2006) Increased expression of the immediate-early gene arc/arg3.1 reduces AMPA receptor-mediated synaptic transmission. Neuron 52:461–474. https://doi.org/10.1016/j.neuron.2006.09.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Rj W, Rs P, Ii BJ, As N (1996) Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons. J Neurosci 16(6):1982–1989. https://doi.org/10.1523/JNEUROSCI.16-06-01982.1996

    Article  Google Scholar 

  47. Suzuki A, Yanagisawa M, Greene RW (2020) Loss of Arc attenuates the behavioral and molecular responses for sleep homeostasis in mice. Proc Natl Acad Sci USA 117:10547–10553. https://doi.org/10.1073/pnas.1906840117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Chowdhury S, Shepherd JD, Okuno H et al (2006) Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron 52:445–459. https://doi.org/10.1016/j.neuron.2006.08.033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. DaSilva LLP, Wall MJ, de Almeida PL et al (2016) Activity-regulated cytoskeleton-associated protein controls AMPAR endocytosis through a direct interaction with clathrin-adaptor protein 2. eNeuro 3:0144-15. https://doi.org/10.1523/ENEURO.0144-15.2016

    Article  Google Scholar 

  50. Wall MJ, Corrêa SAL (2018) The mechanistic link between Arc/Arg3.1 expression and AMPA receptor endocytosis. Semin Cell Dev Biol 77:17–24. https://doi.org/10.1016/j.semcdb.2017.09.005

    Article  CAS  PubMed  Google Scholar 

  51. Beguin S, Crépel V, Aniksztejn L et al (2013) An epilepsy-related ARX polyalanine expansion modifies glutamatergic neurons excitability and morphology without affecting GABAergic neurons development. Cereb Cortex 23:1484–1494. https://doi.org/10.1093/cercor/bhs138

    Article  PubMed  Google Scholar 

  52. Grassart A, Cheng AT, Hong SH et al (2014) Actin and dynamin2 dynamics and interplay during clathrin-mediated endocytosis. J Cell Biol 205:721–735. https://doi.org/10.1083/jcb.201403041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Pulimood NS, Contreras M, Pruitt ME et al (2021) Phosphorylation of CREB at serine 142 and 143 is essential for visual cortex plasticity. eNeuro 8. https://doi.org/10.1523/ENEURO.0217-21.2021

  54. Antonny B, Burd C, De Camilli P et al (2016) Membrane fission by dynamin: what we know and what we need to know. EMBO J 35:2270–2284. https://doi.org/10.15252/embj.201694613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Kjaerulff O, Brodin L, Jung A (2011) The structure and function of endophilin proteins. Cell Biochem Biophys 60:137–154. https://doi.org/10.1007/s12013-010-9137-5

    Article  CAS  PubMed  Google Scholar 

  56. Diering GH, Huganir RL (2018) The AMPA receptor code of synaptic plasticity. Neuron 100:314–329. https://doi.org/10.1016/j.neuron.2018.10.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Burnashev N, Monyer H, Seeburg PH, Sakmann B (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8:189–198. https://doi.org/10.1016/0896-6273(92)90120-3

    Article  CAS  PubMed  Google Scholar 

  58. Livingstone RW, Elder MK et al (2021) Secreted amyloid precursor protein-alpha enhances LTP Through the synthesis and trafficking of Ca2+-permeable AMPA receptors. Front Mol Neurosci 14:660208. https://doi.org/10.3389/fnmol.2021.660208

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Barylko B, Wilkerson JR, Cavalier SH et al (2018) Palmitoylation and membrane binding of Arc/Arg3.1: a potential role in synaptic depression. Biochemistry 57:520–524. https://doi.org/10.1021/acs.biochem.7b00959

    Article  CAS  PubMed  Google Scholar 

  60. de la Peña JB, Barragan-Iglesias P, Lou T-F et al (2021) Intercellular Arc signaling regulates vasodilation. J Neurosci Off J Soc Neurosci 41:7712–7726. https://doi.org/10.1523/JNEUROSCI.0440-21.2021

    Article  Google Scholar 

  61. Babaei P (2021) NMDA and AMPA receptors dysregulation in Alzheimer’s disease. Eur J Pharmacol 908:174310. https://doi.org/10.1016/j.ejphar.2021.174310

    Article  CAS  PubMed  Google Scholar 

  62. Hanada T (2020) Ionotropic glutamate receptors in epilepsy: a review focusing on AMPA and NMDA receptors. Biomolecules 10:464. https://doi.org/10.3390/biom10030464

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Paoletti P (2011) Molecular basis of NMDA receptor functional diversity. Eur J Neurosci 33:1351–1365. https://doi.org/10.1111/j.1460-9568.2011.07628.x

    Article  PubMed  Google Scholar 

  64. Chen L-F, Lyons MR, Liu F et al (2020) The NMDA receptor subunit GluN3A regulates synaptic activity-induced and myocyte enhancer factor 2C (MEF2C)-dependent transcription. J Biol Chem 295:8613–8627. https://doi.org/10.1074/jbc.RA119.010266

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Bye CM, McDonald RJ (2019) A specific role of hippocampal NMDA receptors and Arc protein in rapid encoding of novel environmental representations and a more general long-term consolidation function. Front Behav Neurosci 13:8. https://doi.org/10.3389/fnbeh.2019.00008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Czerniawski J, Ree F, Chia C et al (2011) The importance of having Arc: expression of the immediate-early gene Arc is required for hippocampus-dependent fear conditioning and blocked by NMDA receptor antagonism. J Neurosci Off J Soc Neurosci 31:11200–11207. https://doi.org/10.1523/JNEUROSCI.2211-11.2011

    Article  CAS  Google Scholar 

  67. Chen T, Zhu J, Yang L-K et al (2017) Glutamate-induced rapid induction of Arc/Arg3.1 requires NMDA receptor-mediated phosphorylation of ERK and CREB. Neurosci Lett 661:23–28. https://doi.org/10.1016/j.neulet.2017.09.024

    Article  CAS  PubMed  Google Scholar 

  68. Korb E, Wilkinson CL, Delgado RN et al (2013) Arc in the nucleus regulates PML-dependent GluA1 transcription and homeostatic plasticity. Nat Neurosci 16:874–883. https://doi.org/10.1038/nn.3429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Hedde PN, Barylko B, Binns DD et al (2022) Differential mobility and self-association of Arc/Arg3.1 in the cytoplasm and nucleus of living cells. ACS Chem Neurosci 13:876–882. https://doi.org/10.1021/acschemneuro.1c00744

    Article  CAS  PubMed  Google Scholar 

  70. Korb E, Finkbeiner S (2013) PML in the brain: from development to degeneration. Front Oncol 3:242. https://doi.org/10.3389/fonc.2013.00242

    Article  PubMed  PubMed Central  Google Scholar 

  71. Wee CL, Teo S, Oey NE et al (2014) Nuclear Arc interacts with the histone acetyltransferase Tip60 to modify H4K12 acetylation(1,2,3). eNeuro 1:0019-14. https://doi.org/10.1523/ENEURO.0019-14.2014

    Article  Google Scholar 

  72. Kim T-K, Hemberg M, Gray JM et al (2010) Widespread transcription at neuronal activity-regulated enhancers. Nature 465:182–187. https://doi.org/10.1038/nature09033

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Jin W, Jiang G, Yang Y et al (2022) Animal-eRNAdb: a comprehensive animal enhancer RNA database. Nucleic Acids Res 50:D46–D53. https://doi.org/10.1093/nar/gkab832

    Article  CAS  PubMed  Google Scholar 

  74. Han Z, Li W (2022) Enhancer RNA: what we know and what we can achieve. Cell Proliferation 55(4):e13202. https://doi.org/10.1111/cpr.13202

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Dykes IM, Emanueli C (2017) Transcriptional and post-transcriptional gene regulation by long non-coding RNA. Genom Proteom Bioinform 15:177–186. https://doi.org/10.1016/j.gpb.2016.12.005

    Article  CAS  Google Scholar 

  76. Schaukowitch K, Joo JY, Liu X, Watts JK, Martinez C, Kim TK (2014) Enhancer 21 RNA facilitates NELF release from immediate early genes. Mol Cell 56(1):29–42. https://doi.org/10.1016/j.molcel.2014.08.023

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Andzelm MM, Vanness D, Greenberg ME, Linden DJ (2019) A late phase of long-term synaptic depression in cerebellar Purkinje cells requires activation of MEF2. Cell Rep 26:1089–1097.e3. https://doi.org/10.1016/j.celrep.2019.01.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Wilkerson JR, Tsai N-P, Maksimova MA et al (2014) A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination. Cell Rep 7:1589–1600. https://doi.org/10.1016/j.celrep.2014.04.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Bourtchuladze R, Frenguelli B, Blendy J et al (1994) Deficient long-term memory in mice with a targeted mutation of the cAMP-responsive element-binding protein. Cell 79:59–68. https://doi.org/10.1016/0092-8674(94)90400-6

    Article  CAS  PubMed  Google Scholar 

  80. Flavell SW, Cowan CW et al (2006) Activity-dependent regulation of MEF2 transcription factors suppresses excitatory synapse number. Science (New York, N.Y.) 311(5763):1008–1012. https://doi.org/10.1126/science.1122511

    Article  CAS  PubMed  Google Scholar 

  81. Latusz J, Maćkowiak M (2020) Early-life blockade of NMDA receptors induces epigenetic abnormalities in the adult medial prefrontal cortex: possible involvement in memory impairment in trace fear conditioning. Psychopharmacology 237(1):231–248. https://doi.org/10.1007/s00213-019-05362-5

    Article  CAS  PubMed  Google Scholar 

  82. Kaushik M, Kaushik P, Parvez S (2022) Memory related molecular signatures: the pivots for memory consolidation and Alzheimer’s related memory decline. Ageing Res Rev 76:101577. https://doi.org/10.1016/j.arr.2022.101577

    Article  CAS  PubMed  Google Scholar 

  83. Steven A, Friedrich M, Jank P, Heimer N et al (2020) What turns CREB on? And off? And why does it matter? Cell Mol Life Sci 77(20):4049–4067. https://doi.org/10.1007/s00018-020-03525-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Roy A, Jana M et al (2013) Regulation of cyclic AMP response element binding and hippocampal plasticity-related genes by peroxisome proliferator-activated receptor α. Cell Rep 4(4):724–737. https://doi.org/10.1016/j.celrep.2013.07.028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Kikuchi K, Ihara D, Fukuchi M et al (2019) Involvement of SRF coactivator MKL2 in BDNF-mediated activation of the synaptic activity-responsive element in the Arc gene. J Neurochem 148:204–218. https://doi.org/10.1111/jnc.14596

    Article  CAS  PubMed  Google Scholar 

  86. Tabuchi A, Ihara D (2021) Regulation of dendritic synaptic morphology and transcription by the SRF Cofactor MKL/MRTF. Front Mol Neurosci 14:767842. https://doi.org/10.3389/fnmol.2021.767842

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Pintchovski SA, Peebles CL, Kim HJ, Verdin E, Finkbeiner S (2009) The serum response factor and a putative novel transcription factor regulate expression of the immediate-early gene Arc/Arg3.1 in neurons. The Journal of neuroscience : the official journal of the Society for. Neuroscience 29(5):1525–1537. https://doi.org/10.1523/JNEUROSCI.5575-08.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Wilkinson KA, Henley JM (2010) Mechanisms, regulation and consequences of protein SUMOylation. The Biochem J 428(2):133–145. https://doi.org/10.1042/BJ20100158

    Article  CAS  PubMed  Google Scholar 

  89. Craig TJ, Jaafari N et al (2012) Homeostatic synaptic scaling is regulated by protein SUMOylation. J Biol Chem 287(27):22781–22788. https://doi.org/10.1074/jbc.M112.356337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mabb AM, Ehlers MD (2018) Arc ubiquitination in synaptic plasticity. Semin Cell Dev Biol 77:10–16. https://doi.org/10.1016/j.semcdb.2017.09.009

    Article  CAS  PubMed  Google Scholar 

  91. Gozdz A, Nikolaienko O, Urbanska M et al (2017) GSK3α and GSK3β phosphorylate Arc and regulate its degradation. Front Mol Neurosci 10:192. https://doi.org/10.3389/fnmol.2017.00192

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Popovic D, Vucic D, Dikic I (2014) Ubiquitination in disease pathogenesis and treatment. Nat Med 20:1242–1253. https://doi.org/10.1038/nm.3739

    Article  CAS  PubMed  Google Scholar 

  93. Mabb AM, Je HS, Wall MJ et al (2014) Triad3A regulates synaptic strength by ubiquitination of Arc. Neuron 82:1299–1316. https://doi.org/10.1016/j.neuron.2014.05.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Greer PL, Hanayama R et al (2010) The Angelman syndrome protein Ube3A regulates synapse development by ubiquitinating arc. Cell 140(5):704–716. https://doi.org/10.1016/j.cell.2010.01.02

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Zhang W, Chuang Y-A, Na Y et al (2019) Arc oligomerization is regulated by CaMKII phosphorylation of the GAG domain: an essential mechanism for plasticity and memory formation. Mol Cell 75:13–25.e5. https://doi.org/10.1016/j.molcel.2019.05.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Schnabel R, Palmer MJ, Kilpatrick IC, Collingridge GL (1999) A CaMKII inhibitor, KN-62, facilitates DHPG-induced LTD in the CA1 region of the hippocampus. Neuropharmacology 38:605–608. https://doi.org/10.1016/s0028-3908(98)00229-9

    Article  CAS  PubMed  Google Scholar 

  97. Okuno H, Akashi K, Ishii Y et al (2012) Inverse synaptic tagging of inactive synapses via dynamic interaction of Arc/Arg3.1 with CaMKIIβ. Cell 149:886–898. https://doi.org/10.1016/j.cell.2012.02.062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Bloomer WAC, VanDongen HMA, VanDongen AMJ (2008) Arc/Arg3.1 translation is controlled by convergent N-methyl-D-aspartate and Gs-coupled receptor signaling pathways. J Biol Chem 283:582–592. https://doi.org/10.1074/jbc.M702451200

    Article  CAS  PubMed  Google Scholar 

  99. Messaoudi E, Ying S-W, Kanhema T et al (2002) Brain-derived neurotrophic factor triggers transcription-dependent, late phase long-term potentiation in vivo. J Neurosci Off J Soc Neurosci 22:7453–7461. https://doi.org/10.1523/JNEUROSCI.22-17-07453.2002

    Article  CAS  Google Scholar 

  100. Aicardi G, Argilli E et al (2004) Induction of long-term potentiation and depression is reflected by corresponding changes in secretion of endogenous brain-derived neurotrophic factor. Proc Natl Acad Sci USA 101(44):15788–15792. https://doi.org/10.1073/pnas.0406960101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Kuipers SD, Trentani A, Tiron A et al (2016) BDNF-induced LTP is associated with rapid Arc/Arg3.1-dependent enhancement in adult hippocampal neurogenesis. Sci Rep 6:21222. https://doi.org/10.1038/srep21222

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Ibarra IL, Ratnu VS, Gordillo L et al (2022) Comparative chromatin accessibility upon BDNF stimulation delineates neuronal regulatory elements. Mol Syst Biol 18:e10473. https://doi.org/10.15252/msb.202110473

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Suzuki A, Stern SA, Bozdagi O et al (2011) Astrocyte-neuron lactate transport is required for long-term memory formation. Cell 144:810–823. https://doi.org/10.1016/j.cell.2011.02.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Lundquist AJ, Llewellyn GN, Kishi SH et al (2022) Knockdown of astrocytic monocarboxylate transporter 4 in the motor cortex leads to loss of dendritic spines and a deficit in motor learning. Mol Neurobiol 59:1002–1017. https://doi.org/10.1007/s12035-021-02651-z

    Article  CAS  PubMed  Google Scholar 

  105. Vezzoli E, Calì C et al (2020) Ultrastructural evidence for a role of astrocytes and glycogen-derived lactate in learning-dependent synaptic stabilization. Cereb Cortex 30(4):2114–2127. https://doi.org/10.1093/cercor/bhz226

    Article  CAS  PubMed  Google Scholar 

  106. Timofeev I, Bazhenov M, Avramescu S, Nita DA (2010) Posttraumatic epilepsy: the roles of synaptic plasticity. Neurosci Rev J Bringing Neurobiol Neurol Psychiatry 16:19–27. https://doi.org/10.1177/1073858409333545

    Article  Google Scholar 

  107. Parent JM, Yu TW, Leibowitz RT et al (1997) Dentate granule cell neurogenesis is increased by seizures and contributes to aberrant network reorganization in the adult rat hippocampus. J Neurosci Off J Soc Neurosci 17:3727–3738. https://doi.org/10.1523/JNEUROSCI.17-10-03727.1997

    Article  CAS  Google Scholar 

  108. Janz P, Hauser P et al (2018) Position- and time-dependent Arc expression links neuronal activity to synaptic plasticity during epileptogenesis. Front Cell Neurosci 12:244. https://doi.org/10.3389/fncel.2018.00244

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Kryukov KA, Kim KK, Magazanik LG, Zaitsev AV (2016) Status epilepticus alters hippocampal long-term synaptic potentiation in a rat lithium-pilocarpine model. Neuroreport 27:1191–1195. https://doi.org/10.1097/WNR.0000000000000656

    Article  CAS  PubMed  Google Scholar 

  110. Notenboom RGE, Ramakers GMJ, Kamal A et al (2010) Long-lasting modulation of synaptic plasticity in rat hippocampus after early-life complex febrile seizures. Eur J Neurosci 32:749–758. https://doi.org/10.1111/j.1460-9568.2010.07321.x

    Article  PubMed  Google Scholar 

  111. Jiang Q, Wang J, Wu Y et al (2008) Early-life epileptiform discharges exert both rapid and long-lasting effects on AMPAR subunit composition and distribution in developing neurons. Neurosci Lett 444:31–35. https://doi.org/10.1016/j.neulet.2008.08.006

    Article  CAS  PubMed  Google Scholar 

  112. Menuz K, Nicoll RA (2008) Loss of inhibitory neuron AMPA receptors contributes to ataxia and epilepsy in stargazer mice. J Neurosci Off J Soc Neurosci 28:10599–10603. https://doi.org/10.1523/JNEUROSCI.2732-08.2008

    Article  CAS  Google Scholar 

  113. Mathern GW, Pretorius JK, Kornblum HI et al (1997) Human hippocampal AMPA and NMDA mRNA levels in temporal lobe epilepsy patients. Brain J Neurol 120(Pt 11):1937–1959. https://doi.org/10.1093/brain/120.11.1937

    Article  Google Scholar 

  114. Isokawa M, Levesque M, Fried I, Engel J (1997) Glutamate currents in morphologically identified human dentate granule cells in temporal lobe epilepsy. J Neurophysiol 77:3355–3369. https://doi.org/10.1152/jn.1997.77.6.3355

    Article  CAS  PubMed  Google Scholar 

  115. Cohan CH, Stradecki-Cohan HM et al (2017) Protein kinase C epsilon delays latency until anoxic depolarization through arc expression and GluR2 internalization. J Cereb Blood Flow Metab 37(12):3774–3788. https://doi.org/10.1177/0271678X17712178

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Falcicchia C, Paolone G et al (2018) Seizure-suppressant and neuroprotective effects of encapsulated BDNF-producing cells in a rat model of temporal lobe epilepsy. Mol Ther Methods Clin Dev 9:211–224. https://doi.org/10.1016/j.omtm.2018.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Selkoe DJ, Schenk D (2003) Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol 43:545–584. https://doi.org/10.1146/annurev.pharmtox.43.100901.140248

    Article  CAS  PubMed  Google Scholar 

  118. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356. https://doi.org/10.1126/science.1072994

    Article  CAS  PubMed  Google Scholar 

  119. Rudinskiy N, Hawkes JM, Betensky RA et al (2012) Orchestrated experience-driven Arc responses are disrupted in a mouse model of Alzheimer’s disease. Nat Neurosci 15:1422–1429. https://doi.org/10.1038/nn.3199

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Lacor PN, Buniel MC, Chang L et al (2004) Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. J Neurosci Off J Soc Neurosci 24:10191–10200. https://doi.org/10.1523/JNEUROSCI.3432-04.2004

    Article  CAS  Google Scholar 

  121. Wu J, Petralia RS, Kurushima H et al (2011) Arc/Arg3.1 regulates an endosomal pathway essential for activity-dependent β-amyloid generation. Cell 147. https://doi.org/10.1016/j.cell.2011.09.036

  122. Rao CV, Farooqui M, Zhang Y et al (2018) Spontaneous development of Alzheimer’s disease-associated brain pathology in a shugoshin-1 mouse cohesinopathy model. Aging Cell 17:e12797. https://doi.org/10.1111/acel.12797

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Rao CV, Farooqui M, Madhavaram A et al (2020) GSK3-ARC/Arg3.1 and GSK3-Wnt signaling axes trigger amyloid-β accumulation and neuroinflammation in middle-aged shugoshin 1 mice. Aging Cell 19:e13221. https://doi.org/10.1111/acel.13221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Li Z, Jo J, Jia JM, Lo SC, Whitcomb DJ, Jiao S, Cho K, Sheng M (2010) Caspase-3 activation via mitochondria is required for long-term depression and AMPA receptor internalization. Cell 141(5):859–871. https://doi.org/10.1016/j.cell.2010.03.053

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Hsieh H, Boehm J, Sato C et al (2006) AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron 52:831–843. https://doi.org/10.1016/j.neuron.2006.10.035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Driver JE, Racca C, Cunningham MO et al (2007) Impairment of hippocampal gamma-frequency oscillations in vitro in mice overexpressing human amyloid precursor protein (APP). Eur J Neurosci 26:1280–1288. https://doi.org/10.1111/j.1460-9568.2007.05705.x

    Article  PubMed  Google Scholar 

  127. Palop JJ, Mucke L (2009) Epilepsy and cognitive impairments in Alzheimer disease. Arch Neurol 66. https://doi.org/10.1001/archneurol.2009.15

  128. Kim M, Suh J, Romano D et al (2009) Potential late-onset Alzheimer’s disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity. Hum Mol Genet 18:3987–3996. https://doi.org/10.1093/hmg/ddp323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Lannfelt L, Basun H, Wahlund LO et al (1995) Decreased alpha-secretase-cleaved amyloid precursor protein as a diagnostic marker for Alzheimer’s disease. Nat Med 1:829–832. https://doi.org/10.1038/nm0895-829

    Article  CAS  PubMed  Google Scholar 

  130. Tan VTY, Mockett BG et al (2018) Lentivirus-mediated expression of human secreted amyloid precursor protein-alpha prevents development of memory and plasticity deficits in a mouse model of Alzheimer’s disease. Mol Brain 11(1):7. https://doi.org/10.1186/s13041-018-0348-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Fol R, Braudeau J et al (2016) Viral gene transfer of APPsα rescues synaptic failure in an Alzheimer’s disease mouse model. Acta Neuropathol 131(2):247–266. https://doi.org/10.1007/s00401-015-1498-9

    Article  CAS  PubMed  Google Scholar 

  132. Ryan MM, Morris GP et al (2013) Time-dependent changes in gene expression induced by secreted amyloid precursor protein-alpha in the rat hippocampus. BMC Genom 14:376. https://doi.org/10.1186/1471-2164-14-376

    Article  CAS  Google Scholar 

  133. Mucke L, Abraham CR, Masliah E (1996) Neurotrophic and neuroprotective effects of hAPP in transgenic mice. Ann N Y Acad Sci 777:82–88. https://doi.org/10.1111/j.1749-6632.1996.tb34405.x

    Article  CAS  PubMed  Google Scholar 

  134. Livingstone RW, Elder MK et al (2019) Secreted amyloid precursor protein-alpha promotes Arc protein synthesis in hippocampal neurons. Front Mol Neurosci 12:198. https://doi.org/10.3389/fnmol.2019.00198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Blesa J, Phani S, Jackson-Lewis V, Przedborski S (2012) Classic and new animal models of Parkinson’s disease. J Biomed Biotechnol 2012:845618. https://doi.org/10.1155/2012/845618

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Schober A (2004) Classic toxin-induced animal models of Parkinson’s disease: 6-OHDA and MPTP. Cell Tissue Res 318:215–224. https://doi.org/10.1007/s00441-004-0938-y

    Article  PubMed  Google Scholar 

  137. Blandini F, Nappi G, Tassorelli C, Martignoni E (2000) Functional changes of the basal ganglia circuitry in Parkinson’s disease. Prog Neurobiol 62:63–88. https://doi.org/10.1016/s0301-0082(99)00067-2

    Article  CAS  PubMed  Google Scholar 

  138. Petzinger GM, Holschneider DP, Fisher BE et al (2015) The effects of exercise on dopamine neurotransmission in Parkinson’s disease: targeting neuroplasticity to modulate basal ganglia circuitry. Brain Plast Amst Neth 1:29–39. https://doi.org/10.3233/bpl-150021

    Article  CAS  Google Scholar 

  139. Shepherd JD, Rumbaugh G, Wu J et al (2006) Arc/Arg3.1 mediates homeostatic synaptic scaling of AMPA receptors. Neuron 52:475–484. https://doi.org/10.1016/j.neuron.2006.08.034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Ye Y, Mastwal S, Cao VY et al (1991) (2017) Dopamine is required for activity-dependent amplification of Arc mRNA in developing postnatal frontal cortex. Cereb Cortex N Y N 27:3600–3608. https://doi.org/10.1093/cercor/bhw181

    Article  Google Scholar 

  141. Saito N, Tainaka K, Macpherson T et al (2020) Neurotransmission through dopamine D1 receptors is required for aversive memory formation and Arc activation in the cerebral cortex. Neurosci Res 156:58–65. https://doi.org/10.1016/j.neures.2020.04.006

    Article  CAS  PubMed  Google Scholar 

  142. Brown MTC, Bellone C, Mameli M et al (2010) Drug-driven AMPA receptor redistribution mimicked by selective dopamine neuron stimulation. PloS One 5:e15870. https://doi.org/10.1371/journal.pone.0015870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  143. Gao C, Sun X, Wolf ME (2006) Activation of D1 dopamine receptors increases surface expression of AMPA receptors and facilitates their synaptic incorporation in cultured hippocampal neurons. J Neurochem 98:1664–1677. https://doi.org/10.1111/j.1471-4159.2006.03999.x

    Article  CAS  PubMed  Google Scholar 

  144. Snyder GL, Allen PB, Fienberg AA et al (2000) Regulation of phosphorylation of the GluR1 AMPA receptor in the neostriatum by dopamine and psychostimulants in vivo. J Neurosci Off J Soc Neurosci 20:4480–4488. https://doi.org/10.1523/JNEUROSCI.20-12-04480.2000

    Article  CAS  Google Scholar 

  145. Gomez G, Escande MV, Suarez LM et al (2019) Changes in dendritic spine density and inhibitory perisomatic connectivity onto medium spiny neurons in L-dopa-induced dyskinesia. Mol Neurobiol 56:6261–6275. https://doi.org/10.1007/s12035-019-1515-4

    Article  CAS  PubMed  Google Scholar 

  146. Ryu Y-K, Park H-Y, Go J et al (1996) (2018) Effects of histone acetyltransferase inhibitors on L-DOPA-induced dyskinesia in a murine model of Parkinson’s disease. J Neural Transm Vienna Austria 125:1319–1331. https://doi.org/10.1007/s00702-018-1902-4

    Article  CAS  Google Scholar 

  147. Garcia PC, Real CC, Britto LR (2017) The impact of short and long-term exercise on the expression of Arc and AMPARs during evolution of the 6-hydroxy-dopamine animal model of Parkinson’s disease. J Mol Neurosci MN 61:542–552. https://doi.org/10.1007/s12031-017-0896-y

    Article  CAS  PubMed  Google Scholar 

  148. Lewis DA, Gonzalez-Burgos G (2006) Pathophysiologically based treatment interventions in schizophrenia. Nat Med 12:1016–1022. https://doi.org/10.1038/nm1478

    Article  CAS  PubMed  Google Scholar 

  149. Fromer M, Pocklington AJ, Kavanagh DH et al (2014) De novo mutations in schizophrenia implicate synaptic networks. Nature 506:179–184. https://doi.org/10.1038/nature12929

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  150. Chuang Y-A, Hu T-M, Chen C-H et al (2016) Rare mutations and hypermethylation of the ARC gene associated with schizophrenia. Schizophr Res 176:106–113. https://doi.org/10.1016/j.schres.2016.07.019

    Article  PubMed  Google Scholar 

  151. Rees E, Carrera N, Morgan J et al (2019) Targeted sequencing of 10,198 samples confirms abnormalities in neuronal activity and implicates voltage-gated sodium channels in schizophrenia pathogenesis. Biol Psychiatry 85:554–562. https://doi.org/10.1016/j.biopsych.2018.08.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Managò F, Mereu M, Mastwal S et al (2016) Genetic disruption of Arc/Arg3.1 in mice causes alterations in dopamine and neurobehavioral phenotypes related to schizophrenia. Cell Rep 16:2116–2128. https://doi.org/10.1016/j.celrep.2016.07.044

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Gao X, Grendel J et al (2019) Disturbed prefrontal cortex activity in the absence of schizophrenia-like behavioral dysfunction in Arc/Arg3.1 deficient mice. The Journal of neuroscience : the official journal of the Society for. Neuroscience 39(41):8149–8163. https://doi.org/10.1523/JNEUROSCI.0623-19.2019

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Wiedholz LM, Owens WA, Horton RE et al (2008) Mice lacking the AMPA GluR1 receptor exhibit striatal hyperdopaminergia and “schizophrenia-related” behaviors. Mol Psychiatry 13:631–640. https://doi.org/10.1038/sj.mp.4002056

    Article  CAS  PubMed  Google Scholar 

  155. Weinstein JJ, Chohan MO, Slifstein M et al (2017) Pathway-specific dopamine abnormalities in schizophrenia. Biol Psychiatry 81:31–42. https://doi.org/10.1016/j.biopsych.2016.03.2104

    Article  CAS  PubMed  Google Scholar 

  156. Slifstein M, van de Giessen E, Van Snellenberg J et al (2015) Deficits in prefrontal cortical and extrastriatal dopamine release in schizophrenia: a positron emission tomographic functional magnetic resonance imaging study. JAMA Psychiatry 72:316–324. https://doi.org/10.1001/jamapsychiatry.2014.2414

    Article  PubMed  PubMed Central  Google Scholar 

  157. Guillozet-Bongaarts AL, Hyde TM, Dalley RA et al (2014) Altered gene expression in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 19:478–485. https://doi.org/10.1038/mp.2013.30

    Article  CAS  PubMed  Google Scholar 

  158. Winterer G, Weinberger DR (2004) Genes, dopamine and cortical signal-to-noise ratio in schizophrenia. Trends Neurosci 27:683–690. https://doi.org/10.1016/j.tins.2004.08.002

    Article  CAS  PubMed  Google Scholar 

  159. Simpson EH, Kellendonk C, Kandel E (2010) A possible role for the striatum in the pathogenesis of the cognitive symptoms of schizophrenia. Neuron 65:585–596. https://doi.org/10.1016/j.neuron.2010.02.014

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Granado N, Ortiz O, Suárez LM et al (2008) D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus. Cereb Cortex 18:1–12. https://doi.org/10.1093/cercor/bhm026

    Article  PubMed  Google Scholar 

  161. Li Y, Pehrson AL, Waller JA et al (2015) A critical evaluation of the activity-regulated cytoskeleton-associated protein (Arc/Arg3.1)’s putative role in regulating dendritic plasticity, cognitive processes, and mood in animal models of depression. Front Neurosci 9:279. https://doi.org/10.3389/fnins.2015.00279

    Article  PubMed  PubMed Central  Google Scholar 

  162. Increased gene dosage of Ube3a results in autism traits and decreased glutamate synaptic transmission in mice - PubMed. https://pubmed.ncbi.nlm.nih.gov/21974935/. Accessed 4 Apr 2023

  163. Cao C, Rioult-Pedotti MS, Migani P et al (2013) Impairment of TrkB-PSD-95 signaling in Angelman syndrome. PLoS Biol 11:e1001478. https://doi.org/10.1371/journal.pbio.1001478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Allegrini P, Fronzoni L, Pirino D (2009) The influence of the astrocyte field on neuronal dynamics and synchronization. J Biol Phys 35:413–423. https://doi.org/10.1007/s10867-009-9166-8

    Article  PubMed  PubMed Central  Google Scholar 

  165. Newcombe J, Uddin A, Dove R et al (2008) Glutamate receptor expression in multiple sclerosis lesions. Brain Pathol Zurich Switz 18:52–61. https://doi.org/10.1111/j.1750-3639.2007.00101.x

    Article  Google Scholar 

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Funding

This study was supported by grants from the National Key Research and Development Program of China (2022YFC2503802), the National Natural Science Foundation of China (81974206), the National Multidisciplinary Cooperative Diagnosis and Treatment Capacity Project for Major Diseases of Xiangya Hospital, Central South University (z027001), the Hunan Natural Science Foundation (2022JJ30945), the Innovative Construction Foundation of Hunan Province (2021SK4001), the National Natural Science Foundation of Changsha City, China (kq2208385), the Scientific research project of Health Commission of Hunan Province (B202303076019), and the Natural Science Foundation of China (81401078).

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Authors and Affiliations

  1. Department of Neurology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Yifan Chen, Bo Xiao, Zhaohui Luo & Hongyu Long

  2. Xiangya School of Stomatology, Central South University, Changsha, 410008, Hunan, China

    Yifan Chen

  3. State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Xiaohu Wang

  4. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Bo Xiao, Zhaohui Luo & Hongyu Long

  5. Clinical Research Center for Epileptic Disease of Hunan Province, Central South University, Changsha, Hunan, People’s Republic of China, 410008

    Bo Xiao, Zhaohui Luo & Hongyu Long

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  1. Yifan Chen
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  3. Bo Xiao
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All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Hongyu Long and Zhaohui Luo. Manuscript preparation and editing were performed by Yifan Chen and Xiaohu Wang. Bo Xiao provided financial support. All authors read and approved the final manuscript.

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Chen, Y., Wang, X., Xiao, B. et al. Mechanisms and Functions of Activity-Regulated Cytoskeleton-Associated Protein in Synaptic Plasticity. Mol Neurobiol 60, 5738–5754 (2023). https://doi.org/10.1007/s12035-023-03442-4

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