SYNAPTIC PLASTICITY Local Pathways to Long-Term Change

The specific localization of polyribosomes and certain messenger RNAs (mRNAs) in dendrites allows for the intriguing possibility that neurotransmitters trigger long-lasting, synapse-specific, changes in synaptic efficacy through local regulation of protein synthesis. Such use-dependent modifications of particular neuronal pathways could be critically involved in learning and memory. The specific pathways through which localized mRNA translation is regulated, however, remain unclear, nor has a clear link been established between dendritic protein synthesis and behavior in intact animals. Two studies fill in some blanks. Using mass spectrometry and Western analysis on mRNAs and associated proteins isolated from rat hippocampus or cortex, Angenstein et al. demonstrated that a receptor for activated C kinase, RACK1, was a component of a poly(A)-mRNA-protein complex associated with polysome-bound mRNAs actively undergoing translation. Either stimulating metabotropic glutamate receptors (mGluR) in hippocampal slices or activating protein kinase C ß2 (PKCß2) in vitro enhanced RACK1 and PKCß2 association with the complex. In vitro, exogenous PKCß2 phosphorylated poly(A)-mRNA-associated proteins that were also phosphorylated in vivo. These data, together with the immunocytochemical localization of RACK1 to dendrites (and somata) suggest that mGluR-triggered PKCß2 binding to poly(A)-mRNA-protein complexes is involved in localized regulation of protein synthesis. Miller et al. used transgenic mice with mutated calcium/calmodulin-dependent protein kinase II (CaMKII) 3' untranslated regions to investigate the effects of disrupting CaMKII mRNA targeting to dendrites. In the transgenic mice, CaMKII mRNA was restricted to the soma, dendritic CaMKII was markedly reduced, and both late-phase long-term potentiation (LTP) and behaviors associated with memory consolidation were impaired. These data indicate that local translation is important for dendritic expression of CaMKII and that it contributes to LTP and some forms of memory.

F. Angenstein, A. E. Evans, R. E. Settlage, S. T. Moran, S.-C. Ling, A.Y. Klintsova, J. Shabanowitz, D. F. Hunt, W. T. Greenough, A receptor for activated C kinase is part of messenger ribonucleoprotein complexes associated with polyA-mRNAs in neurons. J. Neurosci. 22, 8827-8837 (2002). [Abstract] [Full Text]

S. Miller, M. Yasuda, J. K. Coats, Y. Jones, M. E. Martone, M. Mayford, Disruption of dendritic translation of CamKII impairs stabilization of synaptic plasticity and memory consolidation. Neuron 36, 507-519 (2002). [Online Journal]

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