The observation that activity-regulated cytoskeletal-associated protein (Arc/Arg3.1) is altered following fear conditioning (Ploski et al., 2008) is relevant to the current study on AMPAR subunit changes, because it is widely accepted that Arc/Arg3.1 regulates AMPAR trafficking (Chowdhury et al., 2006; Rial Verde et al., 2006; Shepherd et al., 2006; Bramham et al., 2008). Rial Verde et al. (2006 showed that upregulation of Arc/Arg3.1 leads to the removal of AMPARs containing GluR2/3-subunits, with less of an effect on recently potentiated synapses containing AMPARs with GluR1/2 subunits. Timed manipulation of Arc/Arg3.1 protein levels through administration of antisense mRNA into the LA indicates that the synaptic plasticity underlying STM is not dependent on the presence of this protein, but Arc/Arg3.1 protein is important for the conversion of STM to LTM (Ploski et al., 2008). When these data are taken together, it is likely that the rise of the GluR1-containing AMPARs that we observed does not depend on Arc/Arg3.1. Instead, the delay in the rise of this protein may be suitable for removing GluR2/3-AMPARs from nonactivated pathways and for re-establishing homeostasis of synaptic activity in the LA, after synapses of the activated pathways become strengthened by fear conditioning.
