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[Abstract Title]. - Society for Neuroscience

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(mGluRs) using their selective agonists. Recent studies revealed that mGluR-LTD is dependent<br />

on activation of postsynaptic protein tyrosine phosphatases (PTPs), which transiently<br />

dephosphorylate tyrosine residues in AMPA receptors (AMPARs) [Moult et al., (2006) J.<br />

Neurosci. 26, 2544-2554]. In the present study we have investigated native AMPARs in<br />

hippocampal brain slices to reveal: (1) the involvement of individual AMPAR subunits in<br />

mGluR-LTD induction, (2) differential changes in AMPAR subunit phosphorylation in mGluR-<br />

LTD and NMDAR-LTD and (3) the role of tyrosine dephosphorylation in AMPAR endocytosis<br />

in mGluR-LTD. Here we show that while both GluR2 and GluR3 AMPAR subunits are tyrosinephosphorylated<br />

at basal (nonpotentiated) activity, only GluR2 is dephosphorylated in mGluR-<br />

LTD. The PTP-dependent tyrosine dephosphorylation of GluR2 is specific <strong>for</strong> mGluR-LTD and<br />

does not occur in NMDAR-LTD. Conversely, while NMDAR-LTD is associated with the<br />

dephosphorylation of GluR1-serine-845, mGluR-LTD does not alter the phosphorylation of this<br />

site. The increased AMPAR endocytosis in mGluR-LTD is PTP-dependent and involves tyrosine<br />

dephosphorylation of cell surface AMPARs. Together, these results indicate that the subunit<br />

selective tyrosine dephosphorylation of surface GluR2 regulates AMPAR internalisation in<br />

mGluR-dependent but not in NMDAR-mediated LTD in the hippocampus.<br />

Disclosures: C.M. Gladding, None; E. Molnar , None; Z.I. Bashir, None; G.L. Collingridge,<br />

None.<br />

Poster<br />

238. LTD: Hippocampus and Cortex<br />

Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm<br />

Program#/Poster#: 238.14/D59<br />

Topic: B.08.f. Long-term depression ( LTD )<br />

Support: Scottish Enterprise (Proof of Concept)<br />

Carlton Pharmaceutics<br />

The Cunningham Trust<br />

<strong>Title</strong>: Proteases induce the expression of long-term depression (LTD)<br />

Authors: *A. P. MALLON 1 , D. G. MACGREGOR 2 , T. W. STONE 3 , H. G. NIMMO 3 ;<br />

1 Brown Univ., MPPB, Providence, RI; 2 Strathclyde Univ., Glasgow, United Kingdom; 3 Glasgow<br />

Univ., Glasgow, United Kingdom

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