Next, we designed experiments that make use of the perfusion channel to elicit local changes that might prompt synapse-to-nucleus-to-synapse signaling, resulting in the transport of molecules back to the perfused region. Arc is an immediate early gene that has received much attention due to the localization of its mRNA at synapses with sustained high frequency stimulation (Steward et al., 1998), linking gene expression changes with localized synaptic changes. Recent evidence shows that ARC protein expression is required for mGluR-dependent long-term depression (Park et al., 2008; Waung et al., 2008). The group I mGluR agonist DHPG increases dendritic ARC protein levels without a requirement for new transcription, suggesting that preexisting Arc transcripts can be rapidly (within 5 min) locally translated (Park et al., 2008; Waung et al., 2008). An increase in Arc transcription has been reported 20 min following global DHPG application (Park et al., 2008), suggesting that that following rapid translation of Arc, there is also an increase in Arc transcription.
