title: PDZ protein mediated activity-dependent LTP/LTD developmental switch at rat retinocollicular synapses.
abstract: The insertion of amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors into the plasma membrane and removal via internalization are essential for regulating synaptic strength, which underlies the basic mechanism of learning and memory. The retinocollicular pathway undergoes synaptic refinement during development and shows a wide variety of long-term synaptic changes; however, still little is known about its underlying molecular regulation. Here we report a rapid developmental long-term potentiation (LTP)/long-term depression (LTD) switch and its intracellular mechanism at the rat retinocollicular pathway from postnatal day 5 (P5) to P14. Before P9, neurons always exhibited LTP, whereas LTD was observed only after P10. Blockade of GluR2/3-glutamate receptor-interacting protein (GRIP)/AMPA-receptor-binding protein (ABP)/protein interacting with C kinase 1 (PICK1) interactions with pep2-SVKI could sustain the LTP after P10. This suggests that the LTP/LTD switch relied on PDZ protein activities. Selective interruption of GluR2/3-PICK1 binding by pep2-EVKI blocked the long-lasting effects of both LTP and LTD, suggesting a role for PICK1 in the maintenance of long-term synaptic plasticity. Interestingly, synaptic expression of GRIP increased more than twofold from P7 to P11, whereas ABP and PICK1 expression levels remained stable. Blockade of spontaneous retinal input suppressed this increase and abolished the LTP/LTD switch. These results suggest that the increased GRIP synaptic expression may be a key regulatory factor in mediating the activity-dependent developmental LTP/LTD switch, whereas PICK1 may be required for both LTP and LTD to maintain their long-term effects.
authors.affiliation: NINDS, National Institutes of Health, Porter Neuroscience Research Center, Bethesda, MD 20892, USA. xuel@ninds.nih.gov
authors.forename: Lei
authors.initials: L
authors.lastname: Xue
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Xianhua
authors.initials: X
authors.lastname: Chen
authors.forename: Junji
authors.initials: J
authors.lastname: Lin
authors.forename: Jian
authors.initials: J
authors.lastname: Shi
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000378:metabolism; D003598:Cytoskeletal Proteins; D005071:Evoked Potentials; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D007700:Kinetics; D017774:Long-Term Potentiation / Q000187:drug effects; D036881:Long-Term Synaptic Depression / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D054731:PDZ Domains; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D055351:Retinal Neurons / Q000187:drug effects / Q000378:metabolism*; D013477:Superior Colliculi / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491308:Grip1 protein, rat; C118486:Grip2 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D009842:Oligopeptides; C498298:PICK1 protein, rat; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2
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