Nucleolar Integrity Is Required for the Maintenance of Long-Term Synaptic Plasticity
Autor: | Juan Marcos Alarcon, Clarice Lee, Joshua M. Splett, Matthew J. Troy-Regier, A. Iván Hernández, Kim D. Allen, Andrei V. Gourov, Jason Wolk, William C. Oxberry, Peng P. Gao, Christopher Harte, Darlene Sylvain, Paula S. van de Nes |
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Rok vydání: | 2014 |
Předmět: |
Poly Adenosine Diphosphate Ribose
Memory Long-Term MAP Kinase Signaling System Nucleolus Long-Term Potentiation Poly (ADP-Ribose) Polymerase-1 Gene Expression lcsh:Medicine Biology Biochemistry Hippocampus Mice Learning and Memory Molecular Cell Biology RNA Ribosomal 28S Gene expression Protein biosynthesis Animals lcsh:Science Protein kinase A Neuronal Plasticity Multidisciplinary Colforsin lcsh:R Biology and Life Sciences RNA Neurochemistry Long-term potentiation Cell Biology Cyclic AMP-Dependent Protein Kinases Cell biology Cellular Neuroscience Synapses Synaptic plasticity lcsh:Q Memory consolidation Cellular Structures and Organelles Poly(ADP-ribose) Polymerases Research Article Neuroscience Synaptic Plasticity |
Zdroj: | PLoS ONE, Vol 9, Iss 8, p e104364 (2014) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | Long-term memory (LTM) formation requires new protein synthesis and new gene expression. Based on our work in Aplysia, we hypothesized that the rRNA genes, stimulation-dependent targets of the enzyme Poly(ADP-ribose) polymerase-1 (PARP-1), are primary effectors of the activity-dependent changes in synaptic function that maintain synaptic plasticity and memory. Using electrophysiology, immunohistochemistry, pharmacology and molecular biology techniques, we show here, for the first time, that the maintenance of forskolin-induced late-phase long-term potentiation (L-LTP) in mouse hippocampal slices requires nucleolar integrity and the expression of new rRNAs. The activity-dependent upregulation of rRNA, as well as L-LTP expression, are poly(ADP-ribosyl)ation (PAR) dependent and accompanied by an increase in nuclear PARP-1 and Poly(ADP) ribose molecules (pADPr) after forskolin stimulation. The upregulation of PARP-1 and pADPr is regulated by Protein kinase A (PKA) and extracellular signal-regulated kinase (ERK)--two kinases strongly associated with long-term plasticity and learning and memory. Selective inhibition of RNA Polymerase I (Pol I), responsible for the synthesis of precursor rRNA, results in the segmentation of nucleoli, the exclusion of PARP-1 from functional nucleolar compartments and disrupted L-LTP maintenance. Taken as a whole, these results suggest that new rRNAs (28S, 18S, and 5.8S ribosomal components)--hence, new ribosomes and nucleoli integrity--are required for the maintenance of long-term synaptic plasticity. This provides a mechanistic link between stimulation-dependent gene expression and the new protein synthesis known to be required for memory consolidation. |
Databáze: | OpenAIRE |
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