Synaptic localization of GluR4-containing AMPARs and Arc during acquisition, extinction, and reacquisition of in vitro classical conditioning.

Data suggest that modulation of synaptic strength by incorporation of GluR4-containing AMPARs occurs during conditioned response (CR) acquisition in an in vitro model of classical conditioning. Here we extend these findings by showing that synaptically localized GluR4 subunits parallels the expression of CRs during conditioning training in which there is differential expression of CRs, such as during acquisition, extinction, and reacquisition. Moreover, colocalization and coimmunoprecipitation data suggest that Arc associates with GluR4-containing AMPARs during these different training procedures. Once induced, Arc remains present in synapses during these phases of conditioning. The results are consistent with the interpretation that synaptic incorporation of GluR4-containing AMPARs supports the expression of CRs in this preparation, and that Arc may be involved in trafficking of GluR4 subunits during conditioning. Moreover, the maintained presence of synaptically localized Arc during all phases of conditioning examined indicates that synapses do not return to their naïve state after extinction and that, given the potential trafficking function of Arc, may facilitate relearning after extinction.