Cycles of transcription and local translation consolidate Arc protein at dendritic sites

Maintenance of long-term memory requires transcription and translation of activity-regulated genes. Many of these are immediate early genes (IEGs) with short-lived mRNAs and proteins, often decaying rapidly after stimulation. It remains unknown how an IEG with rapid mRNA and protein turnover can impact long-lasting changes at the synapses. Here, we imaged the long-term transcription and translation dynamics of an IEG, Arc, important for memory consolidation, after stimulation in individual neurons. We demonstrated that the gene underwent reactivation in the same neuron without an additional stimulus, often at the same allele. The cycling of Arc transcription required protein synthesis. Indeed, phases of Arc translation were coordinated with the transcription cycles. Arc mRNAs from later cycles preferentially localized at dendritic sites marked by previous Arc protein, thereby creating hubs of local protein enrichment, potentially maintained by cycles of dendritic translation. These results identify novel characteristics of an IEG and provide insights into how unstable proteins may be sustained over the long-time scale of memory consolidation.