Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9435155 | Progress in Neurobiology | 2005 | 27 Pages |
Abstract
Interest in BDNF as an activity-dependent modulator of neuronal structure and function in the adult brain has intensified in recent years. Localization of BDNF-TrkB to glutamate synapses makes this system attractive as a dynamic, activity-dependent regulator of excitatory transmission and plasticity. Despite individual breakthroughs, an integrated understanding of BDNF function in synaptic plasticity is lacking. Here, we attempt to distill current knowledge of the molecular mechanisms and function of BDNF in LTP. BDNF activates distinct mechanisms to regulate the induction, early maintenance, and late maintenance phases of LTP. Evidence from genetic and pharmacological approaches is reviewed and tabulated. The specific contribution of BDNF depends on the stimulus pattern used to induce LTP, which impacts the duration and perhaps the subcellular site of BDNF release. Particular attention is given to the role of BDNF as a trigger for protein synthesis-dependent late phase LTP-a process referred to as synaptic consolidation. Recent experiments suggest that BDNF activates synaptic consolidation through transcription and rapid dendritic trafficking of mRNA encoded by the immediate early gene, Arc. A model is proposed in which BDNF signaling at glutamate synapses drives the translation of newly transported (Arc) and locally stored (i.e., αCaMKII) mRNA in dendrites. In this model BDNF tags synapses for mRNA capture, while Arc translation defines a critical window for synaptic consolidation. The biochemical mechanisms by which BDNF regulates local translation are also discussed. Elucidation of these mechanisms should shed light on a range of adaptive brain responses including memory and mood resilience.
Keywords
ACDpKaNGFPLCHFSNMDARmGluRIEGIPSPNT-3PI3KCPEBeEF2eIF4E4E-BPeIF4E binding proteinMNK1phosphatidylinositol-3-OH kinaseUTRCREBAMPARERKCaMKIImTORJnkCRETrpPSDGFPBDNFc-Jun N-terminal kinaseEPSPMAPKArglong-term depressionactinomycin Dcornu ammonishigh-frequency stimulationTrkpostsynaptic densitylong-term potentiationLTPeukaryotic elongation factor-2eukaryotic initiation factor 4Enerve growth factorBrain-derived neurotrophic factorphospholipase Cactivity-regulated cytoskeleton-associated proteinArcMEKLTDuntranslated regionneurotrophin-3mammalian target of rapamycinexcitatory postsynaptic potentialinhibitory postsynaptic potentialtransient receptor potentialgreen fluorescent proteincalcium/calmodulin-dependent protein kinase IImitogen-activated protein kinaseCyclic AMP-dependent protein kinaseExtracellular signal-regulated protein kinaseimmediate early geneN-methyl-d-aspartate (NMDA) receptorMetabotropic glutamate receptor
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Clive R. Bramham, Elhoucine Messaoudi,