Postsynaptic organisation and regulation of excitatory synapses
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Pin, J. P. & Duvoisin, R. The metabotropic glutamate receptors: structure and functions. Neuropharmacology 34, 1–26 (1995).
Pawson, T. & Scott, J. D. Signaling through scaffold, anchoring, and adaptor proteins. Science 278, 2075– 2080 (1997).
Kennedy, M. B. Signal transduction molecules at the glutamatergic postsynaptic membrane. Brain Res. Brain Res. Rev. 26, 243– 257 (1998).
Kim, J. H. & Huganir, R. L. Organization and regulation of proteins at synapses. Curr. Opin. Cell Biol. 11, 248–254 (1999).
Ehlers, M. D., Mammen, A. L., Lau, L. F. & Huganir, R. L. Synaptic targeting of glutamate receptors. Curr. Opin. Cell Biol. 8, 484–489 ( 1996).
Gomperts, S. N. Clustering membrane proteins: it's all coming together with the PSD- 95/SAP90 protein family. Cell 84, 659– 662 (1996).
Sheng, M. PDZs and receptor/channel clustering: rounding up the latest suspects. Neuron 17, 575–578 ( 1996).
Kornau, H. C., Seeburg, P. H. & Kennedy, M. B. Interaction of ion channels and receptors with PDZ domain proteins. Curr. Opin. Neurobiol. 7, 368–373 (1997).
Craven, S. E. & Bredt, D. S. PDZ proteins organize synaptic signaling pathways. Cell 93, 495– 498 (1998).
Doyle, D. A. et al. Crystal structures of a complexed and peptide-free membrane protein-binding domain: molecular basis of peptide recognition by PDZ. Cell 85, 1067–1076 ( 1996).
Songyang, Z. et al. Recognition of unique carboxyl-terminal motifs by distinct PDZ domains. Science 275, 73– 77 (1997).
Cho, K. O., Hunt, C. A. & Kennedy, M. B. The rat brain postsynaptic density fraction contains a homolog of the Drosophila discs-large tumor suppressor protein. Neuron 9, 929–942 ( 1992).
Kistner, U. et al. SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. J. Biol. Chem. 268, 4580–4583 ( 1993).
Lue, R. A., Marfatia, S. M., Branton, D. & Chishti, A. H. Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4. 1. Proc. Natl Acad. Sci. USA 91, 9818– 9822 (1994).
Muller, B. M. et al. Molecular characterization and spatial distribution of SAP97, a novel presynaptic protein homologous to SAP90 and the Drosophila discs-large tumor suppressor protein. J. Neurosci. 15, 2354–2366 (1995).
Brenman, J. E., Christopherson, K. S., Craven, S. E., McGee, A. W. & Bredt, D. S. Cloning and characterization of postsynaptic density 93, a nitric oxide synthase interacting protein. J. Neurosci. 16, 7407–7415 (1996).
Kim, E., Cho, K. O., Rothschild, A. & Sheng, M. Heteromultimerization and NMDA receptor-clustering activity of Chapsyn-110, a member of the PSD-95 family of proteins. Neuron 17 , 103–113 (1996).
Muller, B. M. et al. SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo. Neuron 17, 255–265 (1996).
Lahey, T., Gorczyca, M., Jia, X. X. & Budnik, V. The Drosophila tumor suppressor gene dlg is required for normal synaptic bouton structure . Neuron 13, 823–835 (1994).
Budnik, V. et al. Regulation of synapse structure and function by the Drosophila tumor suppressor gene dlg. Neuron 17, 627–640 (1996).
Tejedor, F. J. et al. Essential role for dlg in synaptic clustering of Shaker K+ channels in vivo. J. Neurosci. 17, 152–159 (1997).
Thomas, U. et al. Synaptic clustering of the cell adhesion molecule fasciclin II by discs-large and its role in the regulation of presynaptic structure. Neuron 19, 787– 799 (1997).
Zito, K., Fetter, R. D., Goodman, C. S. & Isacoff, E. Y. Synaptic clustering of Fascilin II and Shaker: essential targeting sequences and role of Dlg. Neuron 19, 1007– 1016 (1997).
Kornau, H. C., Schenker, L. T., Kennedy, M. B. & Seeburg, P. H. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science 269, 1737– 1740 (1995).
Lau, L. F. et al. Interaction of the N-methyl-d-aspartate receptor complex with a novel synapse-associated protein, SAP102. J. Biol. Chem. 271, 21622–21628 ( 1996).
Niethammer, M., Kim, E. & Sheng, M. Interaction between the C-terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases. J. Neurosci. 16, 2157–2163 (1996).
Mori, H. et al. Role of the carboxy-terminal region of the GluR ɛ2 subunit in synaptic localization of the NMDA receptor channel. Neuron 21, 571–580 ( 1998).
Sprengel, R. et al. Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo. Cell 92, 279–289 (1998).
Steigerwald, F. et al. C-terminal truncation of NR2A subunits impairs synaptic but not extrasynaptic localization of NMDA receptors. J. Neurosci. 20, 4573–4851 ( 2000).
Yamada, Y., Chochi, Y., Ko, J. A., Sobue, K. & Inui, M. Activation of channel activity of the NMDA receptor-PSD-95 complex by guanylate kinase-associated protein (GKAP). FEBS Lett. 458, 295–298 (1999).
Yamada, Y., Chochi, Y., Takamiya, K., Sobue, K. & Inui, M. Modulation of the channel activity of the ɛ2/ζ1-subtype N-methyl d-aspartate receptor by PSD-95. J. Biol. Chem. 274, 6647–6652 ( 1999).
Migaud, M. et al. Enhanced long-term potentiation and impaired learning in mice with mutant postsynaptic density-95 protein. Nature 396, 433–439 (1998). The authors generated transgenic mice that had a targeted deletion after the second PDZ domain in PSD-95. The mutant mice had properly localized NMDA receptors and showed normal NMDA receptor function. However, synaptic plasticity was altered as indicated by an abnormal increase in LTP, which might contribute to the aberrant learning shown by the mutant mice. This study indicates that PSD-95 may organize signalling complexes in a NMDA receptor-mediated cascade distinct from PSD-95-dependent receptor localization.
Brenman, J. E. et al. Interaction of nitric oxide synthase with the postsynaptic density protein PSD-95 and α1-syntrophin mediated by PDZ domains . Cell 84, 757–767 (1996).
Christopherson, K. S., Hillier, B. J., Lim, W. A. & Bredt, D. S. PSD-95 assembles a ternary complex with the N-methyl-d-aspartic acid receptor and a bivalent neuronal NO synthase PDZ domain. J. Biol. Chem. 274, 27467–27473 (1999).
Schuman, E. M. & Madison, D. V. Nitric oxide and synaptic function. Annu. Rev. Neurosci. 17, 153–183 (1994).
Sattler, R. et al. Specific coupling of NMDA receptor activation to nitric oxide neurotoxicity by PSD-95 protein. Science 284, 1845–1848 (1999).
Chen, H. J., Rojas-Soto, M., Oguni, A. & Kennedy, M. B. A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II. Neuron 20, 895–904 (1998).
Kim, J. H., Liao, D., Lau, L. F. & Huganir, R. L. SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family. Neuron 20, 683–691 ( 1998).A novel Ras-GTPase activating protein (synGAP) is found in a complex with NMDA receptors through association with PSD-95. SynGAP contains a C2 domain, which may regulate the functional characteristics of this molecule in response to calcium. SynGAP provides a mechanism by which NMDA receptor activation can be linked to Ras-mediated signalling.
Finkbeiner, S. & Greenberg, M. E. Ca2+-dependent routes to Ras: mechanisms for neuronal survival, differentiation, and plasticity? Neuron 16, 233– 236 (1996).
Niethammer, M. et al. CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90. Neuron 20, 693 –707 (1998).
Furuyashiki, T. et al. Citron, a Rho-target, interacts with PSD-95/SAP-90 at glutamatergic synapses in the thalamus. J. Neurosci. 19, 109–118 (1999).
Zhang, W., Vazquez, L., Apperson, M. & Kennedy, M. B. Citron binds to PSD-95 at glutamatergic synapses on inhibitory neurons in the hippocampus. J. Neurosci. 19, 96– 108 (1999).
Ichtchenko, K. et al. Neuroligin 1: a splice site-specific ligand for β -neurexins. Cell 81, 435– 443 (1995).
Hata, Y., Butz, S. & Sudhof, T. C. CASK: a novel dlg/PSD95 homolog with an N-terminal calmodulin-dependent protein kinase domain identified by interaction with neurexins. J. Neurosci. 16, 2488– 2494 (1996).
Butz, S., Okamoto, M. & Sudhof, T. C. A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain. Cell 94, 773–782 ( 1998).
Jo, K., Derin, R., Li, M. & Bredt, D.S. Characterization of MALS/Velis-1,-2, and-3: a family of mammalian LIN- 7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex. J. Neurosci. 19, 4189 –4199 (1999).
Okamoto, M. & Sudhof, T. C. Mints, Munc18-interacting proteins in synaptic vesicle exocytosis. J. Biol. Chem. 272, 31459–31464 (1997).
Kaech, S. M., Whitfield, C. W. & Kim, S. K. The LIN-2/LIN-7/LIN-10 complex mediates basolateral membrane localization of the C. elegans EGF receptor LET-23 in vulval epithelial cells. Cell 94, 761– 771 (1998).
Kim, E. et al. GKAP, a novel synaptic protein that interacts with the guanylate kinase-like domain of the PSD-95/SAP90 family of channel clustering molecules . J. Cell Biol. 136, 669– 678 (1997).
Takeuchi, M. et al. SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. J. Biol. Chem. 272, 11943–11951 (1997).
Satoh, K. et al. DAP-1, a novel protein that interacts with the guanylate kinase-like domains of hDLG and PSD-95. Genes Cells 2, 415–424 (1997).
Deguchi, M. et al. BEGAIN (brain-enriched guanylate kinase-associated protein), a novel neuronal PSD-95/SAP90-binding protein. J. Biol. Chem. 273, 26269–26272 (1998).
Naisbitt, S. et al. Shank, a novel family of postsynaptic density proteins that binds to the NMDA receptor/PSD-95/GKAP complex and cortactin. Neuron 23, 569–582 ( 1999).Identifies a novel protein (SHANK) that binds to GKAP and is found in a complex with NMDA receptors. SHANK can also form homomeric associations through interaction with an amino-terminal SAM domain. SHANK also binds cortactin, an actin- binding protein, through a proline-rich motif and may couple NMDA receptor activity to the regulation of postsynaptic microfilament structure.
Tu, J. C. et al. Coupling of mGluR/Homer and PSD-95 complexes by the Shank family of postsynaptic density proteins. Neuron 23, 583–592 (1999).SHANK is also identified as a Homer- and mGlu receptor-interacting protein . This observation raises the possibility that NMDA receptors are linked to mGlu receptors through a chain that includes PSD-95, GKAP, SHANK and Homer.
Boeckers, T. M. et al. Proline-rich synapse-associated proteins ProSAP1 and ProSAP2 interact with synaptic proteins of the SAPAP/GKAP family. Biochem. Biophys. Res. Commun. 264, 247–252 (1999).
Brakeman, P. R. et al. Homer: a protein that selectively binds metabotropic glutamate receptors. Nature 386, 284– 288 (1997).
Kato, A., Ozawa, F., Saitoh, Y., Hirai, K. & Inokuchi, K. vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long-term potentiation and synaptogenesis . FEBS Lett. 412, 183–189 (1997).
Shiraishi, Y. et al. Cupidin, an isoform of Homer/Vesl, interacts with the actin cytoskeleton and activated rho family small GTPases and is expressed in developing mouse cerebellar granule cells. J. Neurosci. 19, 8389–8400 (1999).
Bortolotto, Z. A., Bashir, Z. I., Davies, C. H. & Collingridge, G. L. A molecular switch activated by metabotropic glutamate receptors regulates induction of long-term potentiation. Nature 368, 740–743 (1994).
O'Connor, J. J., Rowan, M. J. & Anwyl, R. Long-lasting enhancement of NMDA receptor-mediated synaptic transmission by metabotropic glutamate receptor activation. Nature 367, 557–559 ( 1994).
Wyszynski, M. et al. Competitive binding of α-actinin and calmodulin to the NMDA receptor. Nature 385, 439– 442 (1997).
Ehlers, M. D., Fung, E. T., O'Brien, R. J. & Huganir, R. L. Splice variant-specific interaction of the NMDA receptor subunit NR1 with neuronal intermediate filaments. J. Neurosci. 18, 720–730 (1998).
Lin, J. W. et al. Yotiao: A novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1 . J. Neurosci. 18, 2017– 2027 (1998).
Rosenmund, C. & Westbrook, G. L. Calcium-induced actin depolymerization reduces NMDA channel activity. Neuron 10, 805–814 (1993).
Ehlers, M. D., Zhang, S., Bernhardt, J. P. & Huganir, R. L. Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit. Cell 84, 745– 755 (1996).
Zhang, S., Ehlers, M. D., Bernhardt, J. P., Su, C.-T. & Huganir, R. L. Calmodulin mediates calcium-dependent desensitization of N-methyl-d-aspartate receptors. Neuron 21, 443–453 ( 1998).
Naisbitt, S. et al. Interaction of the postsynaptic density-95/guanylate kinase domain-associated protein complex with a light chain of myosin-V and dynein . J. Neurosci. 20, 4524– 4534 (2000).
Setou, M., Nakagawa, T., Seog, S.-H. & Hirokawa, N. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Science 288, 1796– 1802 (2000).Identifies a novel, neuron-specific microtubule motor protein (KIF17) that is found in a complex with Mint, CASK and NR2B. This protein complex is localized to vesicles, and is proposed to transport NMDA receptors within dendrites. Interestingly, PSD-95 is not associated with this complex, indicating a specific postsynaptic role for PSD-95 in NMDA receptor function.
Dong, H. et al. GRIP: a synaptic PDZ domain-containing protein that interacts with AMPA receptors. Nature 386, 279– 284 (1997).
Srivastava, S. et al. Novel anchorage of GluR2/3 to the postsynaptic density by the AMPA receptor-binding protein ABP. Neuron 21, 581–591 (1998).
Dong, H. et al. Characterization of the glutamate receptor-interacting proteins GRIP1 and GRIP2. J. Neurosci. 19, 6930– 6941 (1999).
Xia, J., Zhang, X., Staudinger, J. & Huganir, R. L. Clustering of AMPA receptors by the synaptic PDZ domain-containing protein PICK1. Neuron 22, 179–187 (1999).
Dev, K. K., Nishimune, A., Henley, J. M. & Nakanishi, S. The protein kinase C α-binding protein PICK1 interacts with short but not long form alternative splice variants of AMPA receptor subunits. Neuropharmacology 38, 635–644 (1999).
Leonard, A. S., Davare, M. A., Horne, M. C., Garner, C. C. & Hell, J. W. SAP97 is associated with the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit. J. Biol. Chem. 273, 19518– 19524 (1998).
Rongo, C., Whitfield, C. W., Rodal, A., Kim, S. K. & Kaplan, J. M. LIN-10 is a shared component of the polarized protein localization pathways in neurons and epithelia. Cell 94, 751–759 ( 1998).This report describes the necessity of a PDZ-containing protein (Lin-10) in correctly localizing the C. elegans glutamate receptor GLR-1 in both neurons and epithelial cells. These data reinforce previous studies indicating that epithelial cells and neurons share some common methods for protein sorting.
Torres, R. et al. PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands. Neuron 21, 1453–1463 (1998).
Bruckner, K. et al. EphrinB ligands recruit GRIP family PDZ adaptor proteins into raft membrane microdomains. Neuron 22, 511 –524 (1999).
Ye, B. et al. GRASP-1: A neuronal RasGEF associated with the AMPA receptor/GRIP complex. Neuron 26, 603– 617 (2000).
O'Brien, R. J. et al. Synaptic clustering of AMPA receptors by the extracellular immediate gene product NARP. Neuron 23, 309–323 (1999).
Osten, P. et al. The AMPA receptor GluR2 C-terminus can mediate a reversible, ATP-dependent interaction with NSF and α- and β-SNAPs . Neuron 21, 99–110 (1998).
Nishimune, A. et al. NSF binding to GluR2 regulates synaptic transmission. Neuron 21, 87–97 ( 1998).
Song, I. et al. Interaction of the N-ethylmaleimide sensitive factor with AMPA receptors. Neuron 21, 393– 400 (1998).
Hosokawa, T., Rusakov, D. A., Bliss, T. V. & Fine, A. Repeated confocal imaging of individual dendritic spines in the living hippocampal slice: evidence for changes in length and orientation associated with chemically induced LTP. J. Neurosci. 15, 5560– 5573 (1995).
Halpain, S., Hipolito, A. & Saffer, L. Regulation of F-actin stability in dendritic spines by glutamate receptors and calcineurin. J. Neurosci. 18, 9835–9844 (1998).
Maletic-Savatic, M., Malinow, R. & Svoboda, K. Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity. Science 283, 1923–1927 (1999).
Bear, M. F. & Malenka, R. C. Synaptic plasticity: LTP and LTD. Curr. Opin. Neurobiol. 4, 389– 399 (1994).
Bear, M. F. & Abraham, W. C. Long-term depression in hippocampus . Annu. Rev. Neurosci. 19, 437– 462 (1996).
Malenka, R. C. & Nicoll, R. A. Long-term potentiation — a decade of progress? Science 285, 1870–1874 (1999).
Zamanillo, D. et al. Importance of AMPA receptors for hippocampal synaptic plasticity but not for spatial learning. Science 284, 1805–1811 (1999).
Roche, K. W., O'Brien, R. J., Mammen, A. L., Bernhardt, J. & Huganir, R. L. Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Neuron 16, 1179–1188 ( 1996).
Barria, A., Derkach, V. & Soderling, T. Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the α-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor. J. Biol. Chem. 272, 32727–32730 (1997).
Mammen, A. L., Kameyama, K., Roche, K. W. & Huganir, R. Phosphorylation of the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit by calcium/calmodulin-dependent kinase II. J. Biol. Chem. 272, 32528–32533 (1997).
Derkach, V., Barria, A. & Soderling, T. R. Ca2+/calmodulin-kinase II enhances channel conductance of α-amino-3- hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. Proc. Natl Acad. Sci. USA 96, 3269–3274 (1999).
Soderling, T. R. & Derkach, V. A. Postsynaptic protein phosphorylation and LTP. Trends Neurosci. 23 , 75–80 (2000).
Lee, H.-K., Barbarosie, M., Kameyama, K., Bear, M. F. & Huganir, R. L. Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity. Nature 405, 955–959 ( 2000).The authors show that changes in synaptic efficacy correlate with changes in the phosphorylation state of the GluR1 AMPA receptor subunit. The induction of LTP results in an increase in the phosphorylation of Ser 831. In contrast, the expression of LTD results in a decrease in the phosphorylation of Ser 845.
Isaac, J. T., Nicoll, R. A. & Malenka, R. C. Evidence for silent synapses: implications for the expression of LTP. Neuron 15, 427– 434 (1995).
Liao, D., Hessler, N. A. & Malinow, R. Activation of postsynaptically silent synapses during pairing-induced LTP in CA1 region of hippocampal slice. Nature 375, 400–404 ( 1995).
Durand, G., Kovalchuk, Y. & Konnerth, A. Long term potentiation and functional synapse induction in developing hippocampus. Nature 381, 71 –75 (1996).
Gomperts, S. N., Rao, A., Craig, A. M., Malenka, R. C. & Nicoll, R. A. Postsynaptically silent synapses in single neuron cultures. Neuron 21, 1443– 1451 (1998).
Nusser, Z. et al. Cell type and pathway dependence of synaptic AMPA receptor number and variability in the hippocampus. Neuron 21 , 545–559 (1998).
Liao, D., Zhang, X., O'Brien, R., Ehlers, M. D. & Huganir, R. L. Regulation of morphological postsynaptic silent synapses in developing hippocampal neurons. Nature Neurosci. 2, 37–43 (1999). Expression of LTP through NMDA receptor activation leads to the acquisition of AMPA receptor responses and a reduction in the number of silent synapses. Here the authors describe a morphological correlate to these observations in cultured neurons. NMDA receptor activation results in an increase in the number of synaptic AMPA receptor clusters, which colocalize with NMDA receptors, indicating that these synapses are no longer silent.
Petralia, R. S. et al. Selective acquisition of AMPA receptors over postnatal development suggests a molecular basis for silent synapses. Nature Neurosci. 2, 31–36 (1999 ).
Shi, S. H. et al. Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284 , 1811–1816 (1999).
Carroll, R. C., Lissin, D. V., von Zastrow, M., Nicoll, R. A. & Malenka, R. C. Rapid redistribution of glutamate receptors contributes to long-term depression in hippocampal cultures. Nature Neurosci. 2, 454–460 (1999).
Luscher, C. et al. Role of AMPA receptor cycling in synaptic transmission and plasticity. Neuron 24, 649– 658 (1999).
Man, Y. H. et al. Regulation of AMPA receptor-mediated synaptic transmission by clathrin-dependent receptor internalization. Neuron 25, 649–662 (2000).
Wang, Y. T. & Linden, D. J. Expression of cerebellar long-term depression requires postsynaptic clathrin-mediated endocytosis. Neuron 25, 635–647 ( 2000).Shows a conclusive link between LTD expression and the internalization of AMPA receptors in cultured Purkinje cells. Internalization of AMPA receptors seems to occur through clathrin-mediated endocytosis. Indeed, stimulating AMPA receptor endocytosis or expressing LTD mutually occlude each other, indicating that the processes are related.
Luthi, A. et al. Hippocampal LTD expression involves a pool of AMPARs regulated by the NSF–GluR2 interaction. Neuron 24, 389–399 (1999).
Hayashi, Y. et al. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Science 287, 2262–2267 (2000). Expression of LTP or increasing the activity of CaMKII results in the delivery of tagged GluR1 AMPA receptors to the synapse surface. Delivery is dependent on a PDZ domain-mediated interaction, as mutating the PDZ domain at the GluR1 carboxyl terminus abolishes efficient delivery.
Li, P. et al. AMPA receptor-PDZ interactions in facilitation of spinal sensory synapses. Nature Neurosci. 2, 972– 977 (1999).
Chung, H. J., Kim, C.-H., Lee, H.-K., Xia, J. & Huganir, R. L. Interaction of the AMPA receptor subunit GluR2/3 with PDZ domains regulates hippocampal long term–depression. Neuron (in the press).
Linden, D. J., Chung, H. J., Xia, J. & Huganir, R. L. Cerebellar long-term depression requires PKC-regulated interactions between GluR2/3 and PDZ domain-containing proteins. Neuron (submitted).
Liu, S.-Q. J. & Cull-Candy, S. G. Synaptic activity at calcium-permeable AMPA receptors induces a switch in receptor subtype. Nature 405, 454– 458 (2000).Describes a novel form of plasticity in cerebellar stellate cells that seems to be due to changes in AMPA receptor-subunit composition. Activation of AMPA receptors results in a decrease in AMPA receptor-mediated calcium permeability, and an increase in the amplitude of excitatory postsynaptic currents. Changes in synaptic efficacy may be due to the activity-induced delivery of AMPA receptors that are not calcium-permeable.