The brain-derived neurotrophic factor enhances synthesis of Arc in synaptoneurosomes.
Protein synthesis in neurons is essential for the consolidation of memory and for the stabilization of activity-dependent forms of synaptic plasticity such as long-term potentiation (LTP). Activity-dependent translation of dendritically localized mRNAs has been proposed to be a critical source of new proteins necessary for synaptic change. mRNA for the activity-regulated cytoskeletal protein, Arc, is transcribed during LTP and learning, and disruption of its translation gives rise to deficits in both. We have found that selective translation of Arc in a synaptoneurosomal preparation is induced by the brain-derived neurotrophic factor, a neurotrophin that is released during high-frequency stimulation patterns used to elicit LTP. This effect involves signaling through the TrkB receptor and is blocked by the N-methyl-d-aspartate-type glutamate receptor antagonist, MK801. The results suggest there is a synergy between neurotrophic and ionotropic mechanisms that may influence the specificity and duration of changes in synaptic efficacy at glutamatergic synapses.
Yin
Yong
Y
Department of Neurobiology, The Scripps Research Institute and The Skaggs Institute for Chemical Biology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Edelman
Gerald M
GM
Vanderklish
Peter W
PW
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis*; D003712:Dendrites / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D015151:Immunoblotting; D017774:Long-Term Potentiation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D009474:Neurons / Q000502:physiology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013569:Synapses / Q000502:physiology*; D015854:Up-Regulation
D019208:Brain-Derived Neurotrophic Factor; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C092069:activity regulated cytoskeletal-associated protein