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Activity induces Arc mRNA degradation that is dependent upon translation and NMDA receptor activation
Author(s) -
Farris Shan L,
Steward Oswald
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.950.1
Subject(s) - arc (geometry) , nmda receptor , messenger rna , translation (biology) , cycloheximide , microbiology and biotechnology , chemistry , stimulation , ampa receptor , receptor , protein biosynthesis , neuroscience , biology , biochemistry , gene , mathematics , geometry
The mRNA for the immediate early gene Arc is induced by synaptic activity or learning experiences. Arc is unique among neuronal mRNAs in that its newly synthesized transcripts are transported into dendrites and accumulate at activated synapses. Localization of Arc mRNA at active synapses is accompanied by Arc mRNA depletion in inactive dendritic domains. Here we assess whether this is due to activity‐dependent degradation. We used an in vivo paradigm where Arc transcription and transport into dendrites is induced by electroconvulsive seizure and subsequent targeting to active synapses is achieved by high frequency stimulation of the medial perforant path. Local blockade of translation with cycloheximide (CHX) led to an overall increase in Arc mRNA, suggesting that Arc mRNA degradation is translation‐dependent. Increases in Arc mRNA following CHX treatment were greatest in the zone of activated synapses, suggesting that degradation is occurring primarily where Arc mRNA is most actively translated. Targeting to active synapses and depletion in inactive dendritic domains was blocked by NMDA receptor antagonist MK801, indicating that NMDA receptors play a role in localization and translation‐dependent mechanisms regulating Arc mRNA. These data indicate that Arc mRNAs are subject to degradation mechanisms that are enhanced by activity and dependent upon active translation and NMDAR activation.[NS12333 to OS]