title: Bursts of high-frequency stimulation trigger rapid delivery of pre-existing alpha-CaMKII mRNA to synapses: a mechanism in dendritic protein synthesis during long-term potentiation in adult awake rats.
abstract: Messenger ribonucleic acid encoding the alpha-subunit of calcium/calmodulin-dependent protein kinase II (camkII) is abundantly and constitutively expressed in dendrites of pyramidal and granule cell neurons of the adult hippocampus. Recent evidence suggests that camkII messenger ribonucleic acid is stored in a translationally dormant state within ribonucleic acid storage granules. Delivery of camkII messenger ribonucleic acid from sites of storage to sites of translation may therefore be a key step in activity-driven dendritic protein synthesis and synaptic plasticity. Here we explored possible camkII trafficking in the context of long-term potentiation in the dentate gyrus of awake, adult rats. Long-term potentiation was induced by patterned high-frequency stimulation, synaptodendrosomes containing pinched-off dendritic spines were obtained from microdissected dentate gyrus, and messenger ribonucleic acid levels were determined by real-time polymerase chain reaction. High-frequency stimulation triggered a rapid 2.5-fold increase in camkII messenger ribonucleic acid levels in the synaptodendrosome fraction. This increase occurred in the absence of camkII upregulation in the homogenate fraction, indicating trafficking of pre-existing messenger ribonucleic acid to synaptodendrosomes. The elevation in camkII messenger ribonucleic acid was paralleled by an increase in protein expression specific to the synaptodendrosome fraction, and followed by depletion of camkII message. Activity-dependent regulation of camkII messenger ribonucleic acid and protein did not require N-methyl-d-aspartate receptor activation. In contrast, N-methyl-d-aspartate receptor activation was required for induction of the immediate early genes zif268 and activity-regulated cytoskeleton-associated protein in dentate gyrus homogenates. The results support a model in which locally stored camkII messenger ribonucleic acid is rapidly transported to dendritic spines and translated during long-term potentiation in behaving rats.
authors.affiliation: Department of Physiology, Locus on Neuroscience, Jonas Lies vei 91, University of Bergen, N-5009 Bergen, Norway.
authors.forename: Bjarte
authors.initials: B
authors.lastname: Håvik
authors.forename: Håvard
authors.initials: H
authors.lastname: Røkke
authors.forename: Kjetil
authors.initials: K
authors.lastname: Bårdsen
authors.forename: Svend
authors.initials: S
authors.lastname: Davanger
authors.forename: Clive R
authors.initials: CR
authors.lastname: Bramham
mesh_terms: D000818:Animals; D030161:Avian Proteins; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D051766:Early Growth Response Protein 1; D004558:Electric Stimulation; D004594:Electrophysiology / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000648:ultrastructure; D006657:Histones / Q000378:metabolism; D017874:Immediate-Early Proteins; D015151:Immunoblotting / Q000379:methods; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008854:Microscopy, Electron / Q000295:instrumentation / Q000379:methods; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018271:Signal Recognition Particle / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D014851:Wakefulness / Q000502:physiology*
chemical_list: D030161:Avian Proteins; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D018691:Excitatory Amino Acid Antagonists; D006657:Histones; D017874:Immediate-Early Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; D012333:RNA, Messenger; D018271:Signal Recognition Particle; D014157:Transcription Factors; D014404:Tubulin; C033652:postsynaptic density proteins; C071033:cytoskeletal p85 protein, chicken; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D010751:Phosphopyruvate Hydratase