New Insights on Retrieval-Induced and Ongoing Memory Consolidation: Lessons from Arc

Figure 1

Hypothetical model of the differential role of Arc expression after the presentation of a novel and a familiar stimulus. In both cases, active Arc expressing cells are presented in which a swift and massive calcium entry through NMDA receptors at synaptic sites induce dramatic increase in Arc mRNA expression through “SARE” activation. Further NMDA receptors activation and increased protein synthesis observed after novelty exposure could induce synaptic activity and translation-dependent Arc mRNA degradation as it was observed after DG-LTP [29]. In the novelty condition, increased TrkB activation through BDNF may lead to increase in actin polymerization and spine growth at potentiated synapses, mechanisms that, in addition to LTP, are thought to underlie the consolidation of novel information [30]. On the other hand, familiarization primes dendrites for mGluR1-LTD and increased Arc protein synthesis [31, 32] arguably after reactivation of the same circuit. In addition to synapse-specific downregulation of surface AMPA receptors, a more global, cell-wide mechanism occurs in which Arc is shuttled to the nucleus and associates with PML bodies to repress GluR1 transcription. Accumulation of Arc in the nucleus has been observed in the hours following novel environment exploration [33] and may also occur after familiar stimulus exposure.