Abstract
Synaptic plasticity represents the long lasting activity-related strengthening or weakening of synaptic transmission, whose well-characterized types are the long term potentiation and depression. Despite this classical definition, however, the molecular mechanisms by which synaptic plasticity may occur appear to be extremely complex and various. The post-synaptic density (PSD) of glutamatergic synapses is a major site for synaptic plasticity processes and alterations of PSD members have been recently implicated in neuropsychiatric diseases where an impairment of synaptic plasticity has also been reported. Among PSD members, scaffolding proteins have been demonstrated to bridge surface receptors with their intracellular effectors and to regulate receptors distribution and localization both at surface membranes and within the PSD. This review will focus on the molecular physiology and pathophysiology of synaptic plasticity processes, which are tuned by scaffolding PSD proteins and their close related partners, through the modulation of receptor localization and distribution at post-synaptic sites. We suggest that, by regulating both the compartmentalization of receptors along surface membrane and their degradation as well as by modulating receptor trafficking into the PSD, postsynaptic scaffolding proteins may contribute to form distinct signaling micro-domains, whose efficacy in transmitting synaptic signals depends on the dynamic stability of the scaffold, which in turn is provided by relative amounts and post-translational modifications of scaffolding members. The putative relevance for neuropsychiatric diseases and possible pathophysiological mechanisms are discussed in the last part of this work.
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Bliss TV, Gardner-Medwin AR (1973) Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol 232(2):357–374
Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44(1):5–21. doi:10.1016/j.neuron.2004.09.012
Boeckers TM (2006) The postsynaptic density. Cell Tissue Res 326(2):409–422. doi:10.1007/s00441-006-0274-5
Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev Neurosci 10(9):647–658. doi:10.1038/nrn2699
Meador-Woodruff JH, Clinton SM, Beneyto M, McCullumsmith RE (2003) Molecular abnormalities of the glutamate synapse in the thalamus in schizophrenia. Ann N Y Acad Sci 1003:75–93
Proctor DT, Coulson EJ, Dodd PR (2010) Reduction in post-synaptic scaffolding PSD-95 and SAP-102 protein levels in the Alzheimer inferior temporal cortex is correlated with disease pathology. J Alzheimer’s Dis JAD 21(3):795–811. doi:10.3233/JAD-2010-100090
Goto Y, Yang CR, Otani S (2010) Functional and dysfunctional synaptic plasticity in prefrontal cortex: roles in psychiatric disorders. Biol Psychiatry 67(3):199–207. doi:10.1016/j.biopsych.2009.08.026
Sheng M, Hoogenraad CC (2007) The postsynaptic architecture of excitatory synapses: a more quantitative view. Annu Rev Biochem 76:823–847. doi:10.1146/annurev.biochem.76.060805.160029
Santucci DM, Raghavachari S (2008) The effects of NR2 subunit-dependent NMDA receptor kinetics on synaptic transmission and CaMKII activation. PLoS Comput Biol 4(10):e1000208. doi:10.1371/journal.pcbi.1000208
Raghavachari S, Lisman JE (2004) Properties of quantal transmission at CA1 synapses. J Neurophysiol 92(4):2456–2467. doi:10.1152/jn.00258.2004
Opazo P, Sainlos M, Choquet D (2012) Regulation of AMPA receptor surface diffusion by PSD-95 slots. Curr Opin Neurobiol 22(3):453–460. doi:10.1016/j.conb.2011.10.010
Chen X, Winters C, Azzam R, Li X, Galbraith JA, Leapman RD, Reese TS (2008) Organization of the core structure of the postsynaptic density. Proc Natl Acad Sci USA 105(11):4453–4458. doi:10.1073/pnas.0800897105
Ehlers MD, Heine M, Groc L, Lee MC, Choquet D (2007) Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity. Neuron 54(3):447–460. doi:10.1016/j.neuron.2007.04.010
Borgdorff AJ, Choquet D (2002) Regulation of AMPA receptor lateral movements. Nature 417(6889):649–653. doi:10.1038/nature00780
Heine M, Groc L, Frischknecht R, Beique JC, Lounis B, Rumbaugh G, Huganir RL, Cognet L, Choquet D (2008) Surface mobility of postsynaptic AMPARs tunes synaptic transmission. Science 320(5873):201–205. doi:10.1126/science.1152089
Sharma K, Fong DK, Craig AM (2006) Postsynaptic protein mobility in dendritic spines: long-term regulation by synaptic NMDA receptor activation. Mol Cell Neurosci 31(4):702–712. doi:10.1016/j.mcn.2006.01.010
Tardin C, Cognet L, Bats C, Lounis B, Choquet D (2003) Direct imaging of lateral movements of AMPA receptors inside synapses. EMBO J 22(18):4656–4665. doi:10.1093/emboj/cdg463
Groc L, Heine M, Cousins SL, Stephenson FA, Lounis B, Cognet L, Choquet D (2006) NMDA receptor surface mobility depends on NR2A-2B subunits. Proc Natl Acad Sci USA 103(49):18769–18774. doi:10.1073/pnas.0605238103
Tomita S, Adesnik H, Sekiguchi M, Zhang W, Wada K, Howe JR, Nicoll RA, Bredt DS (2005) Stargazin modulates AMPA receptor gating and trafficking by distinct domains. Nature 435(7045):1052–1058. doi:10.1038/nature03624
Bats C, Groc L, Choquet D (2007) The interaction between Stargazin and PSD-95 regulates AMPA receptor surface trafficking. Neuron 53(5):719–734. doi:10.1016/j.neuron.2007.01.030
Rumbaugh G, Sia GM, Garner CC, Huganir RL (2003) Synapse-associated protein-97 isoform-specific regulation of surface AMPA receptors and synaptic function in cultured neurons. J Neurosci Off J Soc Neurosci 23(11):4567–4576
Nakagawa T, Futai K, Lashuel HA, Lo I, Okamoto K, Walz T, Hayashi Y, Sheng M (2004) Quaternary structure, protein dynamics, and synaptic function of SAP97 controlled by L27 domain interactions. Neuron 44(3):453–467. doi:10.1016/j.neuron.2004.10.012
Waites CL, Specht CG, Hartel K, Leal-Ortiz S, Genoux D, Li D, Drisdel RC, Jeyifous O, Cheyne JE, Green WN, Montgomery JM, Garner CC (2009) Synaptic SAP97 isoforms regulate AMPA receptor dynamics and access to presynaptic glutamate. J Neurosci Off J Soc Neurosci 29(14):4332–4345. doi:10.1523/JNEUROSCI.4431-08.2009
Malinow R, Malenka RC (2002) AMPA receptor trafficking and synaptic plasticity. Annu Rev Neurosci 25:103–126. doi:10.1146/annurev.neuro.25.112701.142758
Carroll RC, Beattie EC, von Zastrow M, Malenka RC (2001) Role of AMPA receptor endocytosis in synaptic plasticity. Nat Rev Neurosci 2(5):315–324. doi:10.1038/35072500
Lu J, Helton TD, Blanpied TA, Racz B, Newpher TM, Weinberg RJ, Ehlers MD (2007) Postsynaptic positioning of endocytic zones and AMPA receptor cycling by physical coupling of dynamin-3 to Homer. Neuron 55(6):874–889. doi:10.1016/j.neuron.2007.06.041
de Bartolomeis A, Iasevoli F (2003) The Homer family and the signal transduction system at glutamatergic postsynaptic density: potential role in behavior and pharmacotherapy. Psychopharmacol Bull 37(3):51–83
Iasevoli F, Ambesi-Impiombato A, Fiore G, Panariello F, Muscettola G, de Bartolomeis A (2011) Pattern of acute induction of Homer1a gene is preserved after chronic treatment with first- and second-generation antipsychotics: effect of short-term drug discontinuation and comparison with Homer1a-interacting genes. J Psychopharmacol 25(7):875–887. doi:10.1177/0269881109358199
Iasevoli F, Tomasetti C, Marmo F, Bravi D, Arnt J, de Bartolomeis A (2010) Divergent acute and chronic modulation of glutamatergic postsynaptic density genes expression by the antipsychotics haloperidol and sertindole. Psychopharmacology 212(3):329–344
Tomasetti C, Dell’Aversano C, Iasevoli F, Marmo F, de Bartolomeis A (2011) The acute and chronic effects of combined antipsychotic-mood stabilizing treatment on the expression of cortical and striatal postsynaptic density genes. Prog Neuropsychopharmacol Biol Psychiatry 35(1):184–197. doi:10.1016/j.pnpbp.2010.10.025
Bhattacharyya S, Biou V, Xu W, Schluter O, Malenka RC (2009) A critical role for PSD-95/AKAP interactions in endocytosis of synaptic AMPA receptors. Nat Neurosci 12(2):172–181. doi:10.1038/nn.2249
Chowdhury S, Shepherd JD, Okuno H, Lyford G, Petralia RS, Plath N, Kuhl D, Huganir RL, Worley PF (2006) Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron 52(3):445–459. doi:10.1016/j.neuron.2006.08.033
Fumagalli F, Frasca A, Racagni G, Riva MA (2008) Dynamic regulation of glutamatergic postsynaptic activity in rat prefrontal cortex by repeated administration of antipsychotic drugs. Mol Pharmacol 73(5):1484–1490. doi:10.1124/mol.107.043786
Lu W, Ziff EB (2005) PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron 47(3):407–421. doi:10.1016/j.neuron.2005.07.006
Citri A, Bhattacharyya S, Ma C, Morishita W, Fang S, Rizo J, Malenka RC (2010) Calcium binding to PICK1 is essential for the intracellular retention of AMPA receptors underlying long-term depression. J Neurosci Off J Soc Neurosci 30(49):16437–16452. doi:10.1523/JNEUROSCI.4478-10.2010
Hanley LJ, Henley JM (2010) Differential roles of GRIP1a and GRIP1b in AMPA receptor trafficking. Neurosci Lett 485(3):167–172. doi:10.1016/j.neulet.2010.09.003
Kulangara K, Kropf M, Glauser L, Magnin S, Alberi S, Yersin A, Hirling H (2007) Phosphorylation of glutamate receptor interacting protein 1 regulates surface expression of glutamate receptors. J Biol Chem 282(4):2395–2404. doi:10.1074/jbc.M606471200
Jo J, Son GH, Winters BL, Kim MJ, Whitcomb DJ, Dickinson BA, Lee YB, Futai K, Amici M, Sheng M, Collingridge GL, Cho K (2010) Muscarinic receptors induce LTD of NMDAR EPSCs via a mechanism involving hippocalcin, AP2 and PSD-95. Nat Neurosci 13(10):1216–1224. doi:10.1038/nn.2636
Steiner P, Higley MJ, Xu W, Czervionke BL, Malenka RC, Sabatini BL (2008) Destabilization of the postsynaptic density by PSD-95 serine 73 phosphorylation inhibits spine growth and synaptic plasticity. Neuron 60(5):788–802. doi:10.1016/j.neuron.2008.10.014
Verpelli C, Dvoretskova E, Vicidomini C, Rossi F, Chiappalone M, Schoen M, Di Stefano B, Mantegazza R, Broccoli V, Bockers TM, Dityatev A, Sala C (2011) Importance of Shank3 protein in regulating metabotropic glutamate receptor 5 (mGluR5) expression and signaling at synapses. J Biol Chem 286(40):34839–34850. doi:10.1074/jbc.M111.258384
Lennertz L, Wagner M, Wolwer W, Schuhmacher A, Frommann I, Berning J, Schulze-Rauschenbach S, Landsberg MW, Steinbrecher A, Alexander M, Franke PE, Pukrop R, Ruhrmann S, Bechdolf A, Gaebel W, Klosterkotter J, Hafner H, Maier W, Mossner R (2012) A promoter variant of SHANK1 affects auditory working memory in schizophrenia patients and in subjects clinically at risk for psychosis. Eur Arch Psychiatry Clin Neurosci 262(2):117–124. doi:10.1007/s00406-011-0233-3
Delahaye A, Toutain A, Aboura A, Dupont C, Tabet AC, Benzacken B, Elion J, Verloes A, Pipiras E, Drunat S (2009) Chromosome 22q13.3 deletion syndrome with a de novo interstitial 22q13.3 cryptic deletion disrupting SHANK3. Eur J Med Genet 52(5):328–332. doi:10.1016/j.ejmg.2009.05.004
Durand CM, Betancur C, Boeckers TM, Bockmann J, Chaste P, Fauchereau F, Nygren G, Rastam M, Gillberg IC, Anckarsater H, Sponheim E, Goubran-Botros H, Delorme R, Chabane N, Mouren-Simeoni MC, de Mas P, Bieth E, Roge B, Heron D, Burglen L, Gillberg C, Leboyer M, Bourgeron T (2007) Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet 39(1):25–27. doi:10.1038/ng1933
Moessner R, Marshall CR, Sutcliffe JS, Skaug J, Pinto D, Vincent J, Zwaigenbaum L, Fernandez B, Roberts W, Szatmari P, Scherer SW (2007) Contribution of SHANK3 mutations to autism spectrum disorder. Am J Hum Genet 81(6):1289–1297. doi:10.1086/522590
Penzes P, Johnson RC, Alam MR, Kambampati V, Mains RE, Eipper BA (2000) An isoform of kalirin, a brain-specific GDP/GTP exchange factor, is enriched in the postsynaptic density fraction. J Biol Chem 275(9):6395–6403
Penzes P, Cahill ME, Jones KA, VanLeeuwen JE, Woolfrey KM (2011) Dendritic spine pathology in neuropsychiatric disorders. Nat Neurosci 14(3):285–293. doi:10.1038/nn.2741
Penzes P, Johnson RC, Sattler R, Zhang X, Huganir RL, Kambampati V, Mains RE, Eipper BA (2001) The neuronal Rho-GEF Kalirin-7 interacts with PDZ domain-containing proteins and regulates dendritic morphogenesis. Neuron 29(1):229–242
Xie Z, Srivastava DP, Photowala H, Kai L, Cahill ME, Woolfrey KM, Shum CY, Surmeier DJ, Penzes P (2007) Kalirin-7 controls activity-dependent structural and functional plasticity of dendritic spines. Neuron 56(4):640–656. doi:10.1016/j.neuron.2007.10.005
Kiraly DD, Lemtiri-Chlieh F, Levine ES, Mains RE, Eipper BA (2011) Kalirin binds the NR2B subunit of the NMDA receptor, altering its synaptic localization and function. J Neurosci Off J Soc Neurosci 31(35):12554–12565. doi:10.1523/JNEUROSCI.3143-11.2011
Ma XM, Wang Y, Ferraro F, Mains RE, Eipper BA (2008) Kalirin-7 is an essential component of both shaft and spine excitatory synapses in hippocampal interneurons. J Neurosci 28(3):711–724. doi:10.1523/JNEUROSCI.5283-07.2008
Cahill ME, Xie Z, Day M, Photowala H, Barbolina MV, Miller CA, Weiss C, Radulovic J, Sweatt JD, Disterhoft JF, Surmeier DJ, Penzes P (2009) Kalirin regulates cortical spine morphogenesis and disease-related behavioral phenotypes. Proc Natl Acad Sci USA 106(31):13058–13063. doi:10.1073/pnas.0904636106
Ma XM, Kiraly DD, Gaier ED, Wang Y, Kim EJ, Levine ES, Eipper BA, Mains RE (2008) Kalirin-7 is required for synaptic structure and function. J Neurosci 28(47):12368–12382. doi:10.1523/JNEUROSCI.4269-08.2008
Lemtiri-Chlieh F, Zhao L, Kiraly DD, Eipper BA, Mains RE, Levine ES (2011) Kalirin-7 is necessary for normal NMDA receptor-dependent synaptic plasticity. BMC Neurosci 12:126. doi:10.1186/1471-2202-12-126
Kushima I, Nakamura Y, Aleksic B, Ikeda M, Ito Y, Shiino T, Okochi T, Fukuo Y, Ujike H, Suzuki M, Inada T, Hashimoto R, Takeda M, Kaibuchi K, Iwata N, Ozaki N (2012) Resequencing and association analysis of the KALRN and EPHB1 genes and their contribution to schizophrenia susceptibility. Schizophr Bull 38(3):552–560. doi:10.1093/schbul/sbq118
Zhao Y, Hegde AN, Martin KC (2003) The ubiquitin proteasome system functions as an inhibitory constraint on synaptic strengthening. Curr Biol 13(11):887–898
Yashiro K, Riday TT, Condon KH, Roberts AC, Bernardo DR, Prakash R, Weinberg RJ, Ehlers MD, Philpot BD (2009) Ube3a is required for experience-dependent maturation of the neocortex. Nat Neurosci 12(6):777–783. doi:10.1038/nn.2327
Yeh SH, Mao SC, Lin HC, Gean PW (2006) Synaptic expression of glutamate receptor after encoding of fear memory in the rat amygdala. Mol Pharmacol 69(1):299–308. doi:10.1124/mol.105.017194
Mao SC, Lin HC, Gean PW (2008) Augmentation of fear extinction by D-cycloserine is blocked by proteasome inhibitors. Neuropsychopharmacology Off Publ Am Coll Neuropsychopharmacol 33(13):3085–3095. doi:10.1038/npp.2008.30
Dong C, Upadhya SC, Ding L, Smith TK, Hegde AN (2008) Proteasome inhibition enhances the induction and impairs the maintenance of late-phase long-term potentiation. Learn Mem 15(5):335–347. doi:10.1101/lm.984508
Kato A, Rouach N, Nicoll RA, Bredt DS (2005) Activity-dependent NMDA receptor degradation mediated by retrotranslocation and ubiquitination. Proc Natl Acad Sci USA 102(15):5600–5605. doi:10.1073/pnas.0501769102
Jurd R, Thornton C, Wang J, Luong K, Phamluong K, Kharazia V, Gibb SL, Ron D (2008) Mind bomb-2 is an E3 ligase that ubiquitinates the N-methyl-d-aspartate receptor NR2B subunit in a phosphorylation-dependent manner. J Biol Chem 283(1):301–310. doi:10.1074/jbc.M705580200
Mao LM, Wang W, Chu XP, Zhang GC, Liu XY, Yang YJ, Haines M, Papasian CJ, Fibuch EE, Buch S, Chen JG, Wang JQ (2009) Stability of surface NMDA receptors controls synaptic and behavioral adaptations to amphetamine. Nat Neurosci 12(5):602–610. doi:10.1038/nn.2300
Park EC, Glodowski DR, Rongo C (2009) The ubiquitin ligase RPM-1 and the p38 MAPK PMK-3 regulate AMPA receptor trafficking. PLoS ONE 4(1):e4284. doi:10.1371/journal.pone.0004284
Burbea M, Dreier L, Dittman JS, Grunwald ME, Kaplan JM (2002) Ubiquitin and AP180 regulate the abundance of GLR-1 glutamate receptors at postsynaptic elements in C. elegans. Neuron 35(1):107–120
Schaefer H, Rongo C (2006) KEL-8 is a substrate receptor for CUL3-dependent ubiquitin ligase that regulates synaptic glutamate receptor turnover. Mol Biol Cell 17(3):1250–1260. doi:10.1091/mbc.E05-08-0794
Pavlopoulos E, Trifilieff P, Chevaleyre V, Fioriti L, Zairis S, Pagano A, Malleret G, Kandel ER (2011) Neuralized1 activates CPEB3: a function for nonproteolytic ubiquitin in synaptic plasticity and memory storage. Cell 147(6):1369–1383. doi:10.1016/j.cell.2011.09.056
Lee SH, Choi JH, Lee N, Lee HR, Kim JI, Yu NK, Choi SL, Kim H, Kaang BK (2008) Synaptic protein degradation underlies destabilization of retrieved fear memory. Science 319(5867):1253–1256. doi:10.1126/science.1150541
Spangler SA, Hoogenraad CC (2007) Liprin-alpha proteins: scaffold molecules for synapse maturation. Biochem Soc Trans 35(Pt 5):1278–1282. doi:10.1042/BST0351278
Wyszynski M, Kim E, Dunah AW, Passafaro M, Valtschanoff JG, Serra-Pages C, Streuli M, Weinberg RJ, Sheng M (2002) Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron 34(1):39–52
van Roessel P, Elliott DA, Robinson IM, Prokop A, Brand AH (2004) Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell 119(5):707–718. doi:10.1016/j.cell.2004.11.028
Hoogenraad CC, Feliu-Mojer MI, Spangler SA, Milstein AD, Dunah AW, Hung AY, Sheng M (2007) Liprinalpha1 degradation by calcium/calmodulin-dependent protein kinase II regulates LAR receptor tyrosine phosphatase distribution and dendrite development. Dev Cell 12(4):587–602. doi:10.1016/j.devcel.2007.02.006
Djakovic SN, Schwarz LA, Barylko B, DeMartino GN, Patrick GN (2009) Regulation of the proteasome by neuronal activity and calcium/calmodulin-dependent protein kinase II. J Biol Chem 284(39):26655–26665. doi:10.1074/jbc.M109.021956
Bingol B, Wang CF, Arnott D, Cheng D, Peng J, Sheng M (2010) Autophosphorylated CaMKIIalpha acts as a scaffold to recruit proteasomes to dendritic spines. Cell 140(4):567–578. doi:10.1016/j.cell.2010.01.024
Colledge M, Snyder EM, Crozier RA, Soderling JA, Jin Y, Langeberg LK, Lu H, Bear MF, Scott JD (2003) Ubiquitination regulates PSD-95 degradation and AMPA receptor surface expression. Neuron 40(3):595–607
Guo L, Wang Y (2007) Glutamate stimulates glutamate receptor interacting protein 1 degradation by ubiquitin-proteasome system to regulate surface expression of GluR2. Neuroscience 145(1):100–109. doi:10.1016/j.neuroscience.2006.11.042
Yang H, Takagi H, Konishi Y, Ageta H, Ikegami K, Yao I, Sato S, Hatanaka K, Inokuchi K, Seog DH, Setou M (2008) Transmembrane and ubiquitin-like domain-containing protein 1 (Tmub1/HOPS) facilitates surface expression of GluR2-containing AMPA receptors. PLoS ONE 3(7):e2809. doi:10.1371/journal.pone.0002809
Dodd PR, Scott HL, Westphalen RI (1994) Excitotoxic mechanisms in the pathogenesis of dementia. Neurochem Int 25(3):203–219
Gong Y, Lippa CF (2010) Review: disruption of the postsynaptic density in Alzheimer’s disease and other neurodegenerative dementias. Am J Alzheimers Dis Other Demen 25(7):547–555. doi:10.1177/1533317510382893
Ehlers MD (2003) Activity level controls postsynaptic composition and signaling via the ubiquitin-proteasome system. Nat Neurosci 6(3):231–242. doi:10.1038/nn1013
Sjostrom PJ, Rancz EA, Roth A, Hausser M (2008) Dendritic excitability and synaptic plasticity. Physiol Rev 88(2):769–840. doi:10.1152/physrev.00016.2007
Almeida CG, Tampellini D, Takahashi RH, Greengard P, Lin MT, Snyder EM, Gouras GK (2005) Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Neurobiol Dis 20(2):187–198. doi:10.1016/j.nbd.2005.02.008
Louneva N, Cohen JW, Han LY, Talbot K, Wilson RS, Bennett DA, Trojanowski JQ, Arnold SE (2008) Caspase-3 is enriched in postsynaptic densities and increased in Alzheimer’s disease. Am J Pathol 173(5):1488–1495. doi:10.2353/ajpath.2008.080434
Lacor PN, Buniel MC, Chang L, Fernandez SJ, Gong Y, Viola KL, Lambert MP, Velasco PT, Bigio EH, Finch CE, Krafft GA, Klein WL (2004) Synaptic targeting by Alzheimer’s-related amyloid beta oligomers. J Neurosci 24(45):10191–10200. doi:10.1523/JNEUROSCI.3432-04.2004
Gong Y, Lippa CF, Zhu J, Lin Q, Rosso AL (2009) Disruption of glutamate receptors at Shank-postsynaptic platform in Alzheimer’s disease. Brain Res 1292:191–198. doi:10.1016/j.brainres.2009.07.056
Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML, Garcia-Alloza M, Micheva KD, Smith SJ, Kim ML, Lee VM, Hyman BT, Spires-Jones TL (2009) Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci U S A 106(10):4012–4017. doi:10.1073/pnas.0811698106
Roselli F, Tirard M, Lu J, Hutzler P, Lamberti P, Livrea P, Morabito M, Almeida OF (2005) Soluble beta-amyloid1-40 induces NMDA-dependent degradation of postsynaptic density-95 at glutamatergic synapses. J Neurosci 25(48):11061–11070. doi:10.1523/JNEUROSCI.3034-05.2005
Gylys KH, Fein JA, Yang F, Wiley DJ, Miller CA, Cole GM (2004) Synaptic changes in Alzheimer’s disease: increased amyloid-beta and gliosis in surviving terminals is accompanied by decreased PSD-95 fluorescence. Am J Pathol 165(5):1809–1817
Leuba G, Savioz A, Vernay A, Carnal B, Kraftsik R, Tardif E, Riederer I, Riederer BM (2008) Differential changes in synaptic proteins in the Alzheimer frontal cortex with marked increase in PSD-95 postsynaptic protein. J Alzheimer’s Dis JAD 15(1):139–151
Nyffeler M, Zhang WN, Feldon J, Knuesel I (2007) Differential expression of PSD proteins in age-related spatial learning impairments. Neurobiol Aging 28(1):143–155. doi:10.1016/j.neurobiolaging.2005.11.003
Shao CY, Mirra SS, Sait HB, Sacktor TC, Sigurdsson EM (2011) Postsynaptic degeneration as revealed by PSD-95 reduction occurs after advanced Abeta and tau pathology in transgenic mouse models of Alzheimer’s disease. Acta Neuropathol 122(3):285–292. doi:10.1007/s00401-011-0843-x
Roselli F, Livrea P, Almeida OF (2011) CDK5 is essential for soluble amyloid beta-induced degradation of GKAP and remodeling of the synaptic actin cytoskeleton. PLoS ONE 6(7):e23097. doi:10.1371/journal.pone.0023097
Roselli F, Hutzler P, Wegerich Y, Livrea P, Almeida OF (2009) Disassembly of shank and homer synaptic clusters is driven by soluble beta-amyloid(1–40) through divergent NMDAR-dependent signalling pathways. PLoS ONE 4(6):e6011. doi:10.1371/journal.pone.0006011
Dickey CA, Loring JF, Montgomery J, Gordon MN, Eastman PS, Morgan D (2003) Selectively reduced expression of synaptic plasticity-related genes in amyloid precursor protein + presenilin-1 transgenic mice. J Neurosci 23(12):5219–5226
Clemmensen C, Aznar S, Knudsen GM, Klein AB (2012) The microtubule-associated protein 1A (MAP1A) is an early molecular target of soluble abeta-peptide. Cell Mol Neurobiol 32(4):561–566. doi:10.1007/s10571-011-9796-9
Youn H, Ji I, Ji HP, Markesbery WR, Ji TH (2007) Under-expression of Kalirin-7 increases iNOS activity in cultured cells and correlates to elevated iNOS activity in Alzheimer’s disease hippocampus. J Alzheimers Dis 12(3):271–281
Blanpied TA, Ehlers MD (2004) Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological disease. Biol Psychiatry 55(12):1121–1127. doi:10.1016/j.biopsych.2003.10.006
Pfeiffer BE, Huber KM (2009) The state of synapses in fragile X syndrome. Neuroscientist 15(5):549–567. doi:10.1177/1073858409333075
Muddashetty RS, Kelic S, Gross C, Xu M, Bassell GJ (2007) Dysregulated metabotropic glutamate receptor-dependent translation of AMPA receptor and postsynaptic density-95 mRNAs at synapses in a mouse model of fragile X syndrome. J Neurosci 27(20):5338–5348. doi:10.1523/JNEUROSCI.0937-07.2007
Bassell GJ, Warren ST (2008) Fragile X syndrome: loss of local mRNA regulation alters synaptic development and function. Neuron 60(2):201–214. doi:10.1016/j.neuron.2008.10.004
Luscher C, Huber KM (2010) Group 1 mGluR-dependent synaptic long-term depression: mechanisms and implications for circuitry and disease. Neuron 65(4):445–459. doi:10.1016/j.neuron.2010.01.016
Dolen G, Bear MF (2008) Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. J Physiol 586(6):1503–1508. doi:10.1113/jphysiol.2008.150722
Zalfa F, Eleuteri B, Dickson KS, Mercaldo V, De Rubeis S, di Penta A, Tabolacci E, Chiurazzi P, Neri G, Grant SG, Bagni C (2007) A new function for the fragile X mental retardation protein in regulation of PSD-95 mRNA stability. Nat Neurosci 10(5):578–587. doi:10.1038/nn1893
Tarpey P, Parnau J, Blow M, Woffendin H, Bignell G, Cox C, Cox J, Davies H, Edkins S, Holden S, Korny A, Mallya U, Moon J, O’Meara S, Parker A, Stephens P, Stevens C, Teague J, Donnelly A, Mangelsdorf M, Mulley J, Partington M, Turner G, Stevenson R, Schwartz C, Young I, Easton D, Bobrow M, Futreal PA, Stratton MR, Gecz J, Wooster R, Raymond FL (2004) Mutations in the DLG3 gene cause nonsyndromic X-linked mental retardation. Am J Hum Genet 75(2):318–324. doi:10.1086/422703
Zanni G, van Esch H, Bensalem A, Saillour Y, Poirier K, Castelnau L, Ropers HH, de Brouwer AP, Laumonnier F, Fryns JP, Chelly J (2010) A novel mutation in the DLG3 gene encoding the synapse-associated protein 102 (SAP102) causes non-syndromic mental retardation. Neurogenetics 11(2):251–255. doi:10.1007/s10048-009-0224-y
Cuthbert PC, Stanford LE, Coba MP, Ainge JA, Fink AE, Opazo P, Delgado JY, Komiyama NH, O’Dell TJ, Grant SG (2007) Synapse-associated protein 102/dlgh3 couples the NMDA receptor to specific plasticity pathways and learning strategies. J Neurosci 27(10):2673–2682. doi:10.1523/JNEUROSCI.4457-06.2007
Chen BS, Thomas EV, Sanz-Clemente A, Roche KW (2011) NMDA receptor-dependent regulation of dendritic spine morphology by SAP102 splice variants. J Neurosci 31(1):89–96. doi:10.1523/JNEUROSCI.1034-10.2011
Hung AY, Futai K, Sala C, Valtschanoff JG, Ryu J, Woodworth MA, Kidd FL, Sung CC, Miyakawa T, Bear MF, Weinberg RJ, Sheng M (2008) Smaller dendritic spines, weaker synaptic transmission, but enhanced spatial learning in mice lacking Shank1. J Neurosci 28(7):1697–1708. doi:10.1523/JNEUROSCI.3032-07.2008
Berkel S, Tang W, Trevino M, Vogt M, Obenhaus HA, Gass P, Scherer SW, Sprengel R, Schratt G, Rappold GA (2012) Inherited and de novo SHANK2 variants associated with autism spectrum disorder impair neuronal morphogenesis and physiology. Hum Mol Genet 21(2):344–357. doi:10.1093/hmg/ddr470
Durand CM, Perroy J, Loll F, Perrais D, Fagni L, Bourgeron T, Montcouquiol M, Sans N (2012) SHANK3 mutations identified in autism lead to modification of dendritic spine morphology via an actin-dependent mechanism. Mol Psychiatry 17(1):71–84. doi:10.1038/mp.2011.57
Bangash MA, Park JM, Melnikova T, Wang D, Jeon SK, Lee D, Syeda S, Kim J, Kouser M, Schwartz J, Cui Y, Zhao X, Speed HE, Kee SE, Tu JC, Hu JH, Petralia RS, Linden DJ, Powell CM, Savonenko A, Xiao B, Worley PF (2011) Enhanced polyubiquitination of Shank3 and NMDA receptor in a mouse model of autism. Cell 145(5):758–772. doi:10.1016/j.cell.2011.03.052
Ichtchenko K, Nguyen T, Sudhof TC (1996) Structures, alternative splicing, and neurexin binding of multiple neuroligins. J Biol Chem 271(5):2676–2682
Tabuchi K, Blundell J, Etherton MR, Hammer RE, Liu X, Powell CM, Sudhof TC (2007) A neuroligin-3 mutation implicated in autism increases inhibitory synaptic transmission in mice. Science 318(5847):71–76. doi:10.1126/science.1146221
Mondin M, Labrousse V, Hosy E, Heine M, Tessier B, Levet F, Poujol C, Blanchet C, Choquet D, Thoumine O (2011) Neurexin-neuroligin adhesions capture surface-diffusing AMPA receptors through PSD-95 scaffolds. J Neurosci 31(38):13500–13515. doi:10.1523/JNEUROSCI.6439-10.2011
Tabrizi SJ, Cleeter MW, Xuereb J, Taanman JW, Cooper JM, Schapira AH (1999) Biochemical abnormalities and excitotoxicity in Huntington’s disease brain. Ann Neurol 45(1):25–32
Vonsattel JP, DiFiglia M (1998) Huntington disease. J Neuropathol Exp Neurol 57(5):369–384
Trottier Y, Lutz Y, Stevanin G, Imbert G, Devys D, Cancel G, Saudou F, Weber C, David G, Tora L et al (1995) Polyglutamine expansion as a pathological epitope in Huntington’s disease and four dominant cerebellar ataxias. Nature 378(6555):403–406. doi:10.1038/378403a0
Hodgson JG, Agopyan N, Gutekunst CA, Leavitt BR, LePiane F, Singaraja R, Smith DJ, Bissada N, McCutcheon K, Nasir J, Jamot L, Li XJ, Stevens ME, Rosemond E, Roder JC, Phillips AG, Rubin EM, Hersch SM, Hayden MR (1999) A YAC mouse model for Huntington’s disease with full-length mutant huntingtin, cytoplasmic toxicity, and selective striatal neurodegeneration. Neuron 23(1):181–192
Shehadeh J, Fernandes HB, Zeron Mullins MM, Graham RK, Leavitt BR, Hayden MR, Raymond LA (2006) Striatal neuronal apoptosis is preferentially enhanced by NMDA receptor activation in YAC transgenic mouse model of Huntington disease. Neurobiol Dis 21(2):392–403. doi:10.1016/j.nbd.2005.08.001
Fan MM, Fernandes HB, Zhang LY, Hayden MR, Raymond LA (2007) Altered NMDA receptor trafficking in a yeast artificial chromosome transgenic mouse model of Huntington’s disease. J Neurosci 27(14):3768–3779. doi:10.1523/JNEUROSCI.4356-06.2007
Sun Y, Savanenin A, Reddy PH, Liu YF (2001) Polyglutamine-expanded huntingtin promotes sensitization of N-methyl-d-aspartate receptors via post-synaptic density 95. J Biol Chem 276(27):24713–24718. doi:10.1074/jbc.M103501200
Fan J, Cowan CM, Zhang LY, Hayden MR, Raymond LA (2009) Interaction of postsynaptic density protein-95 with NMDA receptors influences excitotoxicity in the yeast artificial chromosome mouse model of Huntington’s disease. J Neurosci 29(35):10928–10938. doi:10.1523/JNEUROSCI.2491-09.2009
Hallett PJ, Dunah AW, Ravenscroft P, Zhou S, Bezard E, Crossman AR, Brotchie JM, Standaert DG (2005) Alterations of striatal NMDA receptor subunits associated with the development of dyskinesia in the MPTP-lesioned primate model of Parkinson’s disease. Neuropharmacology 48(4):503–516. doi:10.1016/j.neuropharm.2004.11.008
Picconi B, Centonze D, Rossi S, Bernardi G, Calabresi P (2004) Therapeutic doses of l-dopa reverse hypersensitivity of corticostriatal D2-dopamine receptors and glutamatergic overactivity in experimental parkinsonism. Brain 127(Pt 7):1661–1669. doi:10.1093/brain/awh190
Gardoni F, Picconi B, Ghiglieri V, Polli F, Bagetta V, Bernardi G, Cattabeni F, Di Luca M, Calabresi P (2006) A critical interaction between NR2B and MAGUK in L-DOPA induced dyskinesia. J Neurosci 26(11):2914–2922. doi:10.1523/JNEUROSCI.5326-05.2006
Cartier AE, Djakovic SN, Salehi A, Wilson SM, Masliah E, Patrick GN (2009) Regulation of synaptic structure by ubiquitin C-terminal hydrolase L1. J Neurosci Off J Soc Neurosci 29(24):7857–7868. doi:10.1523/JNEUROSCI.1817-09.2009
Shimura H, Hattori N, Kubo S, Mizuno Y, Asakawa S, Minoshima S, Shimizu N, Iwai K, Chiba T, Tanaka K, Suzuki T (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25(3):302–305. doi:10.1038/77060
Joch M, Ase AR, Chen CX, MacDonald PA, Kontogiannea M, Corera AT, Brice A, Seguela P, Fon EA (2007) Parkin-mediated monoubiquitination of the PDZ protein PICK1 regulates the activity of acid-sensing ion channels. Mol Biol Cell 18(8):3105–3118. doi:10.1091/mbc.E05-11-1027
Helton TD, Otsuka T, Lee MC, Mu Y, Ehlers MD (2008) Pruning and loss of excitatory synapses by the parkin ubiquitin ligase. Proc Natl Acad Sci USA 105(49):19492–19497. doi:10.1073/pnas.0802280105
Park JS, Bateman MC, Goldberg MP (1996) Rapid alterations in dendrite morphology during sublethal hypoxia or glutamate receptor activation. Neurobiol Dis 3(3):215–227
Aarts MM, Tymianski M (2004) Molecular mechanisms underlying specificity of excitotoxic signaling in neurons. Curr Mol Med 4(2):137–147
Sattler R, Xiong Z, Lu WY, Hafner M, MacDonald JF, Tymianski M (1999) Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science 284(5421):1845–1848
Aarts M, Liu Y, Liu L, Besshoh S, Arundine M, Gurd JW, Wang YT, Salter MW, Tymianski M (2002) Treatment of ischemic brain damage by perturbing NMDA receptor- PSD-95 protein interactions. Science 298(5594):846–850. doi:10.1126/science.1072873
Cui H, Hayashi A, Sun HS, Belmares MP, Cobey C, Phan T, Schweizer J, Salter MW, Wang YT, Tasker RA, Garman D, Rabinowitz J, Lu PS, Tymianski M (2007) PDZ protein interactions underlying NMDA receptor-mediated excitotoxicity and neuroprotection by PSD-95 inhibitors. J Neurosci 27(37):9901–9915. doi:10.1523/JNEUROSCI.1464-07.2007
Bratane BT, Cui H, Cook DJ, Bouley J, Tymianski M, Fisher M (2011) Neuroprotection by freezing ischemic penumbra evolution without cerebral blood flow augmentation with a postsynaptic density-95 protein inhibitor. Stroke 42(11):3265–3270. doi:10.1161/STROKEAHA.111.618801
Sun HS, Doucette TA, Liu Y, Fang Y, Teves L, Aarts M, Ryan CL, Bernard PB, Lau A, Forder JP, Salter MW, Wang YT, Tasker RA, Tymianski M (2008) Effectiveness of PSD95 inhibitors in permanent and transient focal ischemia in the rat. Stroke 39(9):2544–2553. doi:10.1161/STROKEAHA.107.506048
Zhou L, Li F, Xu HB, Luo CX, Wu HY, Zhu MM, Lu W, Ji X, Zhou QG, Zhu DY (2010) Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95. Nat Med 16(12):1439–1443. doi:10.1038/nm.2245
Kirov G, Pocklington AJ, Holmans P, Ivanov D, Ikeda M, Ruderfer D, Moran J, Chambert K, Toncheva D, Georgieva L, Grozeva D, Fjodorova M, Wollerton R, Rees E, Nikolov I, Lagemaat LN, Bayes A, Fernandez E, Olason PI, Bottcher Y, Komiyama NH, Collins MO, Choudhary J, Stefansson K, Stefansson H, Grant SG, Purcell S, Sklar P, O’Donovan MC, Owen MJ (2012) De novo CNV analysis implicates specific abnormalities of postsynaptic signalling complexes in the pathogenesis of schizophrenia. Mol Psychiatry 17(2):142–153. doi:10.1038/mp.2011.154
Clinton SM, Meador-Woodruff JH (2004) Abnormalities of the NMDA receptor and associated intracellular molecules in the thalamus in schizophrenia and bipolar disorder. Neuropsychopharmacology 29(7):1353–1362. doi:10.1038/sj.npp.1300451
Clinton SM, Haroutunian V, Davis KL, Meador-Woodruff JH (2003) Altered transcript expression of NMDA receptor-associated postsynaptic proteins in the thalamus of subjects with schizophrenia. Am J Psychiatry 160(6):1100–1109
Ohnuma T, Kato H, Arai H, Faull RL, McKenna PJ, Emson PC (2000) Gene expression of PSD95 in prefrontal cortex and hippocampus in schizophrenia. NeuroReport 11(14):3133–3137
Dracheva S, Marras SA, Elhakem SL, Kramer FR, Davis KL, Haroutunian V (2001) N-methyl-d-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia. Am J Psychiatry 158(9):1400–1410
Cheng MC, Lu CL, Luu SU, Tsai HM, Hsu SH, Chen TT, Chen CH (2010) Genetic and functional analysis of the DLG4 gene encoding the post-synaptic density protein 95 in schizophrenia. PLoS ONE 5(12):e15107. doi:10.1371/journal.pone.0015107
Spellmann I, Rujescu D, Musil R, Mayr A, Giegling I, Genius J, Zill P, Dehning S, Opgen-Rhein M, Cerovecki A, Hartmann AM, Schafer M, Bondy B, Muller N, Moller HJ, Riedel M (2011) Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients. J Psychiatr Res 45(2):234–241. doi:10.1016/j.jpsychires.2010.06.004
Deo AJ, Cahill ME, Li S, Goldszer I, Henteleff R, Vanleeuwen JE, Rafalovich I, Gao R, Stachowski EK, Sampson AR, Lewis DA, Penzes P, Sweet RA (2012) Increased expression of Kalirin-9 in the auditory cortex of schizophrenia subjects: its role in dendritic pathology. Neurobiol Dis 45(2):796–803. doi:10.1016/j.nbd.2011.11.003
Kammermeier PJ (2008) Endogenous homer proteins regulate metabotropic glutamate receptor signaling in neurons. J Neurosci 28(34):8560–8567. doi:10.1523/JNEUROSCI.1830-08.2008
Sala C, Piech V, Wilson NR, Passafaro M, Liu G, Sheng M (2001) Regulation of dendritic spine morphology and synaptic function by Shank and Homer. Neuron 31(1):115–130
Sala C, Futai K, Yamamoto K, Worley PF, Hayashi Y, Sheng M (2003) Inhibition of dendritic spine morphogenesis and synaptic transmission by activity-inducible protein Homer1a. J Neurosci 23(15):6327–6337
Celikel T, Marx V, Freudenberg F, Zivkovic A, Resnik E, Hasan MT, Licznerski P, Osten P, Rozov A, Seeburg PH, Schwarz MK (2007) Select overexpression of homer1a in dorsal hippocampus impairs spatial working memory. Front Neurosci 1(1):97–110. doi:10.3389/neuro.01.1.1.007.2007
Ueta Y, Yamamoto R, Sugiura S, Inokuchi K, Kato N (2008) Homer 1a suppresses neocortex long-term depression in a cortical layer-specific manner. J Neurophysiol 99(2):950–957. doi:10.1152/jn.01101.2007
Bertaso F, Roussignol G, Worley P, Bockaert J, Fagni L, Ango F (2010) Homer1a-dependent crosstalk between NMDA and metabotropic glutamate receptors in mouse neurons. PLoS ONE 5(3):e9755. doi:10.1371/journal.pone.0009755
Gerstein H, O’Riordan K, Osting S, Schwarz M, Burger C (2012) Rescue of synaptic plasticity and spatial learning deficits in the hippocampus of Homer1 knockout mice by recombinant Adeno-associated viral gene delivery of Homer1c. Neurobiol Learn Mem 97(1):17–29. doi:10.1016/j.nlm.2011.08.009
Szumlinski KK, Lominac KD, Kleschen MJ, Oleson EB, Dehoff MH, Schwarz MK, Seeburg PH, Worley PF, Kalivas PW (2005) Behavioral and neurochemical phenotyping of Homer1 mutant mice: possible relevance to schizophrenia. Genes Brain Behav 4(5):273–288. doi:10.1111/j.1601-183X.2005.00120.x
Hennou S, Kato A, Schneider EM, Lundstrom K, Gahwiler BH, Inokuchi K, Gerber U, Ehrengruber MU (2003) Homer-1a/Vesl-1S enhances hippocampal synaptic transmission. Eur J Neurosci 18(4):811–819
Inoue N, Nakao H, Migishima R, Hino T, Matsui M, Hayashi F, Nakao K, Manabe T, Aiba A, Inokuchi K (2009) Requirement of the immediate early gene vesl-1S/homer-1a for fear memory formation. Mol Brain 2:7. doi:10.1186/1756-6606-2-7
Tronson NC, Guzman YF, Guedea AL, Huh KH, Gao C, Schwarz MK, Radulovic J (2010) Metabotropic glutamate receptor 5/Homer interactions underlie stress effects on fear. Biol Psychiatry 68(11):1007–1015. doi:10.1016/j.biopsych.2010.09.004
Okvist A, Fagergren P, Whittard J, Garcia-Osta A, Drakenberg K, Horvath MC, Schmidt CJ, Keller E, Bannon MJ, Hurd YL (2011) Dysregulated postsynaptic density and endocytic zone in the amygdala of human heroin and cocaine abusers. Biol Psychiatry 69(3):245–252. doi:10.1016/j.biopsych.2010.09.037
Blanpied TA, Kerr JM, Ehlers MD (2008) Structural plasticity with preserved topology in the postsynaptic protein network. Proc Natl Acad Sci USA 105(34):12587–12592. doi:10.1073/pnas.0711669105
Newpher TM, Ehlers MD (2009) Spine microdomains for postsynaptic signaling and plasticity. Trends Cell Biol 19(5):218–227. doi:10.1016/j.tcb.2009.02.004
de Bartolomeis A, Sarappa C, Magara S, Iasevoli F (2012) Targeting glutamate system for novel antipsychotic approaches: relevance for residual psychotic symptoms and treatment resistant schizophrenia. Eur J Pharmacol 682(1–3):1–11. doi:10.1016/j.ejphar.2012.02.033
Zhang J, Vinuela A, Neely MH, Hallett PJ, Grant SG, Miller GM, Isacson O, Caron MG, Yao WD (2007) Inhibition of the dopamine D1 receptor signaling by PSD-95. J Biol Chem 282(21):15778–15789. doi:10.1074/jbc.M611485200
Yano M, Steiner H (2005) Methylphenidate (Ritalin) induces Homer 1a and zif 268 expression in specific corticostriatal circuits. Neuroscience 132(3):855–865. doi:10.1016/j.neuroscience.2004.12.019
Iasevoli F, Fiore G, Cicale M, Muscettola G, de Bartolomeis A (2010) Haloperidol induces higher Homer1a expression than risperidone, olanzapine and sulpiride in striatal sub-regions. Psychiatry Res 177(1–2):255–260. doi:10.1016/j.psychres.2010.02.009
Abbas AI, Yadav PN, Yao WD, Arbuckle MI, Grant SG, Caron MG, Roth BL (2009) PSD-95 is essential for hallucinogen and atypical antipsychotic drug actions at serotonin receptors. J Neurosci 29(22):7124–7136. doi:10.1523/JNEUROSCI.1090-09.2009
Tomasetti C, Dell’Aversano C, Iasevoli F, de Bartolomeis A (2007) Homer splice variants modulation within cortico-subcortical regions by dopamine D2 antagonists, a partial agonist, and an indirect agonist: implication for glutamatergic postsynaptic density in antipsychotics action. Neuroscience 150(1):144–158. doi:10.1016/j.neuroscience.2007.08.022
Ambesi-Impiombato A, Panariello F, Dell’aversano C, Tomasetti C, Muscettola G, de Bartolomeis A (2007) Differential expression of Homer 1 gene by acute and chronic administration of antipsychotics and dopamine transporter inhibitors in the rat forebrain. Synapse 61(6):429–439. doi:10.1002/syn.20385
Lominac KD, Oleson EB, Pava M, Klugmann M, Schwarz MK, Seeburg PH, During MJ, Worley PF, Kalivas PW, Szumlinski KK (2005) Distinct roles for different Homer1 isoforms in behaviors and associated prefrontal cortex function. J Neurosci 25(50):11586–11594. doi:10.1523/JNEUROSCI.3764-05.2005
Cook DJ, Teves L, Tymianski M (2012) Treatment of stroke with a PSD-95 inhibitor in the gyrencephalic primate brain. Nature 483(7388):213–217. doi:10.1038/nature10841
Bach A, Clausen BH, Moller M, Vestergaard B, Chi CN, Round A, Sorensen PL, Nissen KB, Kastrup JS, Gajhede M, Jemth P, Kristensen AS, Lundstrom P, Lambertsen KL, Stromgaard K (2012) A high-affinity, dimeric inhibitor of PSD-95 bivalently interacts with PDZ1-2 and protects against ischemic brain damage. Proc Natl Acad Sci USA 109(9):3317–3322. doi:10.1073/pnas.1113761109
Thorsen TS, Madsen KL, Rebola N, Rathje M, Anggono V, Bach A, Moreira IS, Stuhr-Hansen N, Dyhring T, Peters D, Beuming T, Huganir R, Weinstein H, Mulle C, Stromgaard K, Ronn LC, Gether U (2010) Identification of a small-molecule inhibitor of the PICK1 PDZ domain that inhibits hippocampal LTP and LTD. Proc Natl Acad Sci USA 107(1):413–418. doi:10.1073/pnas.0902225107
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Iasevoli, F., Tomasetti, C. & de Bartolomeis, A. Scaffolding Proteins of the Post-synaptic Density Contribute to Synaptic Plasticity by Regulating Receptor Localization and Distribution: Relevance for Neuropsychiatric Diseases. Neurochem Res 38, 1–22 (2013). https://doi.org/10.1007/s11064-012-0886-y
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DOI: https://doi.org/10.1007/s11064-012-0886-y