PDF《Neuropharmacology》

AS, Angelman syndrome;

AS-ODN, antisense oligodeoxynucleotide;

BDNF, brain- derived neurotrophic factor;

CA, cornu ammonis;

CaMKII, Ca2- and calmodulin- dependent protein kinase II;

cdk, cyclin-dependent kinase;

CREB, cAMP response element-binding protein;

CYFIP, cytoplasmic FMRP-interacting protein;

DG, dentate gyrus;

DSCR, Down syndrome critical region;

4EBP, eIF4E-binding protein;

eEF, eukaryotic elongation factor;

eIF, eukaryotic initiation factor;

E-LTP, early-LTP;

FMRP, fragile X mental retardation protein;

GAB1, Grb2-associated binding protein 1;

GFP, green-?uorescent protein;

HFS, high-frequency stimulation;

hnRNP, heter- ogenous nuclear ribonucleoprotein;

IEG, immediate-early gene;

IP3, inositol 1,4,5- trisphosphate;

LIMK1, LIM domain kinase 1;

L-LTP, late-LTP;

LTD, long-term depression;

LTP, long-term potentiation;

MAP, microtubule-associated protein;

MEK1/2, MAPK and ERK kinase, type 1/ 2;

miRNA, microRNA;

MNK, MAP-kinase interacting kinase;

mTOR, mammalian target of rapamycin;

PAK, p21-activated kinase;

PDZ, postsynaptic density-95/Discs large/zona occludens-1;

PI3-K, phos- phatidylinositol 3-kinase;

PLC, phospholipase C;

PKM, protein kinase M;

PRP, plasticity-related protein;

PSD, postsynaptic density;

PSD95, postsynaptic density protein 95;

PSI, protein synthesis-inhibitor;

RISC, RNA-induced silencing complex;

S6K, p70 S6 kinase;

TBS, theta-burst stimulation;

TORC, target of rapamycin (TOR) complex;

TSC, tuberous sclerosis protein;

TrkB, tropomyosin-related kinase B;

YFP, yellow ?uorescent protein;

ZIP, zeta inhibitory peptide. * Corresponding author. Department of Biomedicine, University of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway. Tel.: ?47

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64 10. E-mail address: [email protected] (C.R. Bramham). Contents lists available at SciVerse ScienceDirect Neuropharmacology journal homepage: www.elsevier.com/locate/neuropharm 0028-3908/$ e see front matter ?

2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neuropharm.2013.06.024 Neuropharmacology

76 (2014) 664e676 TrkB regulation of dendritic spine cytoskeletal dynamics. Finally, we seek to understand the functional relationships between these mechanisms and outline the major outstanding issues. 2. BDNF as a trigger for protein synthesis-dependent late LTP Classically, LTP maintenance is split into early and late phases in which only the late, stable phase is blocked by protein synthesis inhibitors (PSIs) (Krug et al., 1984;

Stanton and Sarvey, 1984;

Frey et al., 1988;

Otani et al., 1989;

Matthies et al., 1990;

Abraham and Williams, 2008;

Mayford et al., 2012). As underscored by Routtenberg (2008), the use of PSIs to de?ne the physiological role of protein synthesis has signi?cant caveats. By rapidly inhibiting almost all cellular protein synthesis, it is not surprising that PSIs have deleterious impacts on cellular function that ultimately lead to apoptosis, even in the absence of any immediate effects of the drug on basal synaptic transmission. PSIs also ........