Local synthesis of proteins at synaptic sites on dendrites: role in synaptic plasticity and memory consolidation?
Long-lasting forms of memory are thought to be mediated by modifications in synapses that are induced by particular patterns of activity, take time to be established (consolidated), and involve new gene expression. The molecular mechanisms underlying such long-lasting synaptic modifications remain to be defined. Here, we focus on new findings regarding synapse-specific gene expression and especially the intracellular transport and synaptic targeting of the mRNA for a recently identified immediate early gene called activity-regulated cytoskeleton-associated protein (Arc). Arc mRNA is transported into dendrites after episodes of neuronal activation. The newly synthesized Arc mRNA localizes selectively at synapses that have experienced particular patterns of activity, and this targeting depends on NMDA receptor activation. Arc protein is assembled into the postsynaptic junction, and Arc expression is strongly induced by brief behavioral experiences in select populations of neurons. These features of Arc induction and trafficking reveal novel cellular mechanisms that are well suited to mediate long-term synapse-specific modifications. We will review findings from other laboratories that both LTP and memory are disrupted when Arc induction is blocked, and we will discuss the possibility that Arc protein may play a key role in activity-dependent synaptic modification.
Steward
Oswald
O
Reeve-Irvine Research Center, Department of Anatomy/Neurobiology, College of Medicine, University of California at Irvine, 92697, USA. osteward@uci.edu
Worley
Paul
P
D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D003712:Dendrites / Q000378:metabolism*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017403:In Situ Hybridization; D008568:Memory / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009473:Neuronal Plasticity / Q000502:physiology*; D018075:RNA, Complementary / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D009435:Synaptic Transmission / Q000502:physiology*
D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D018075:RNA, Complementary; D012333:RNA, Messenger; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; C092069:activity regulated cytoskeletal-associated protein