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Arc  is a unique immediate early gene whose expression is induced as synapses are being modified during learning. The uniqueness comes from the fact that newly synthesized  Arc  mRNA is rapidly transported throughout dendrites where it localizes near synapses that were recently activated. Here, we summarize aspects of  Arc  mRNA translation in dendrites  in vivo , focusing especially on features of its expression that are paradoxical or that donot fit in with current models of how Arc protein operates. Findings from  in vivo  studies that donot quite fit include: (1) Following induction of LTP  in vivo ,  Arc  mRNA and protein localize near active synapses, but are also distributed throughout dendrites. In contrast,  Arc  mRNA localizes selectively near active synapses when stimulation is continued as  Arc  mRNA is transported into dendrites; (2) Strong induction of  Arc  expression as a result of a seizure does not lead to a rundown of synaptic efficacy  in vivo  as would be predicted by the hypothesis that high levels of Arc cause glutamate receptor endocytosis and LTD. (3)  Arc  protein is synthesized in the perinuclear cytoplasm rapidly after transcriptional activation, indicating that at least a pool of  Arc  mRNA is not translationally repressed to allow for dendritic delivery; (4) Increases in  Arc  mRNA in dendrites are not paralleled by increases in levels of exon junction complex (EJC) proteins. These results of studies of mRNA trafficking in neurons  in vivo  provide a new perspective on the possible roles of Arc in activity-dependent synaptic modifications.

Localization and local translation of Arc/Arg3.1 mRNA at synapses: some observations and paradoxes