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This Article Full Text Full Text (PDF) All Versions of this Article: 98/3/1278    most recent 00212.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mokin, M. Articles by Keifer, J. Search for Related Content PubMed PubMed Citation Articles by Mokin, M. Articles by Keifer, J.

Conversion of Silent Synapses Into the Active Pool by Selective GluR1-3 and GluR4 AMPAR Trafficking During In Vitro Classical Conditioning

Neuroscience Group, Division of Basic Biomedical Sciences; University of South Dakota School of Medicine; Vermillion, South Dakota

Submitted 27 February 2007; accepted in final form 25 June 2007

The conversion of silent synapses into active sites is hypothesized to be a primary mechanism underlying learning and memory processes. Here we used an in vitro model of classical conditioning from turtles that demonstrates a neural correlate of eyeblink conditioning to examine whether the conversion of silent synapses has a role in this form of associative learning. This was accomplished by direct visualization of AMPA receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) subunits colocalized with synaptophysin (Syn) using immunofluorescence and confocal microscopy. In naive preparations, there was a relatively high level of synapses immunopositive for NR1-Syn alone interpreted to be silent synapses. After early stages of conditioning during acquisition of conditioned responses (CRs), there was a significant increase in the colocalization of GluR1-3 AMPAR subunits at NR1-immunopositive synaptic sites. Later in conditioning, levels of GluR1-3 declined and enhanced colocalization of GluR4-containing AMPAR subunits at synapses was observed. The trafficking of these subunits during conditioning was NMDAR mediated and was accompanied by protein synthesis of GluR4 subunits. Examination of the postsynaptic density fraction confirmed the early and late synaptic insertion of GluR1-3 and GluR4, respectively, during conditioning. These findings suggest that there is differential trafficking of synaptic AMPARs during classical conditioning. Existing GluR1-3 AMPAR subunits are initially delivered to silent synapses early in conditioning to unsilence them followed by synthesis and insertion of GluR4 AMPAR subunits that are required for acquisition and expression of CRs.