Unraveling the molecular mechanisms governing long-term synaptic plasticity is a key to understanding how the brain stores information in neural circuits and adapts to a changing environment. Brain-derived neurotrophic factor (BDNF) has emerged as a regulator of stable, late phase long-term potentiation (L-LTP) at excitatory glutamatergic synapses in the adult brain. However, the mechanisms by which BDNF triggers L-LTP are controversial. Here, we distill and discuss the latest advances along three main lines: 1) TrkB receptor-coupled translational control underlying dendritic protein synthesis and L-LTP, 2) Mechanisms for BDNF-induced rescue of L-LTP when protein synthesis is blocked, and 3) BDNF-TrkB regulation of actin cytoskeletal dynamics in dendritic spines. Finally, we explore the inter-relationships between BDNF-regulated mechanisms, how these mechanisms contribute to different forms of L-LTP in the hippocampus and dentate gyrus, and outline outstanding issues for future research. This article is part of the Special Issue entitled 'BDNF Regulation of Synaptic Structure, Function, and Plasticity'.
Keywords: 4EBP; AS; AS-ODN; Angelman syndrome; Arc; BDNF; Brain-derived neurotrophic factor (BDNF); CA; CREB; CYFIP; Ca2- and calmodulin-dependent protein kinase II; CaMKII; Cytoskeletal dynamics; DG; DSCR; Down syndrome critical region; E-LTP; FMRP; GAB1; GFP; Grb2-associated binding protein 1; HFS; IEG; IP3; L-LTP; LIM domain kinase 1; LIMK1; LTD; LTP; Long-term potentiation (LTP); MAP; MAP-kinase interacting kinase; MAPK and ERK kinase, type 1/ 2; MEK1/2; MNK; PAK; PDZ; PI3-K; PKM; PLC; PRP; PSD; PSD95; PSI; Protein synthesis; RISC; RNA-induced silencing complex; S6K; Synaptic plasticity; TBS; TORC; TSC; Translation control; TrkB; TrkB signaling; YFP; ZIP; activity-regulated cytoskeleton-associated protein; antisense oligodeoxynucleotide; brain-derived neurotrophic factor; cAMP response element-binding protein; cdk; cornu ammonis; cyclin-dependent kinase; cytoplasmic FMRP-interacting protein; dentate gyrus; eEF; eIF; eIF4E-binding protein; early-LTP; eukaryotic elongation factor; eukaryotic initiation factor; fragile X mental retardation protein; green-fluorescent protein; heterogenous nuclear ribonucleoprotein; high-frequency stimulation; hnRNP; immediate-early gene; inositol 1,4,5-trisphosphate; late-LTP; long-term depression; long-term potentiation; mTOR; mammalian target of rapamycin; miRNA; microRNA; microtubule-associated protein; p21-activated kinase; p70 S6 kinase; phosphatidylinositol 3-kinase; phospholipase C; plasticity-related protein; postsynaptic density; postsynaptic density protein 95; postsynaptic density-95/Discs large/zona occludens-1; protein kinase M; protein synthesis-inhibitor; target of rapamycin (TOR) complex; theta-burst stimulation; tropomyosin-related kinase B; tuberous sclerosis protein; yellow fluorescent protein; zeta inhibitory peptide.
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