Neurone specific regulation of dendritic spines in vivo by post synaptic density 95 protein (PSD-95)

被引:66
作者
Vickers, CA
Stephens, B
Bowen, J
Arbuthnott, GW
Grant, SGN
Ingham, CA
机构
[1] Univ Edinburgh, Dept Preclin Vet Sci, RDSVS, Edinburgh EH9 1QH, Midlothian, Scotland
[2] Univ Edinburgh, Dept Neurosci, Edinburgh EH8 9JZ, Midlothian, Scotland
[3] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England
基金
英国惠康基金;
关键词
mouse; synapse; NMDA receptor; plasticity;
D O I
10.1016/j.brainres.2006.03.075
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Post synaptic density protein 95 (PSD-95) is a postsynaptic adaptor protein coupling the NMDA receptor to downstream signalling pathways underlying plasticity. Mice carrying a targeted gene mutation of PSD-95 show altered behavioural plasticity including spatial learning, neuropathic pain, orientation preference in visual cortical cells, and cocaine sensitisation. These behavioural effects are accompanied by changes in long-term potentiation of synaptic transmission. In vitro studies of PSD-95 signalling indicate that it may play a role in regulating dendritic spine structure. Here, we show that PSD-95 mutant mice have alterations in dendritic spine density in the striaturn (a 15% decrease along the dendritic length) and in the hippocampus (a localised 40% increase) without changes in dendritic branch patterns or gross neuronal architecture. These changes in spine density were accompanied by altered expression of proteins known to interact with PSD-95, including NR2B and SAP102, suggesting that PSD-95 plays a role in regulating the expression and activation of proteins found within the NMDA receptor complex. Thus, PSD-95 is an important regulator of neuronal structure as well as plasticity in vivo.
引用
收藏
页码:89 / 98
页数:10
相关论文
共 39 条
[1]   THE 3-DIMENSIONAL ORGANIZATION OF THE HIPPOCAMPAL-FORMATION - A REVIEW OF ANATOMICAL DATA [J].
AMARAL, DG ;
WITTER, MP .
NEUROSCIENCE, 1989, 31 (03) :571-591
[2]   Electron microscopic immunocytochemical detection of PSD-95, PSD-93, SAP-102, and SAP-97 at postsynaptic, presynaptic, and nonsynaptic sites of adult and neonatal rat visual cortex [J].
Aoki, C ;
Miko, I ;
Oviedo, H ;
Mikeladze-Dvali, T ;
Alexandre, L ;
Sweeney, N ;
Bredt, DS .
SYNAPSE, 2001, 40 (04) :239-257
[3]  
BOLAM JP, 1987, POSSIBLE SITES TRANS
[4]  
BOLAM JP, 1990, COMBINED MORPHOLOGIC
[5]   Stargazin regulates synaptic targeting of AMPA receptors by two distinct mechanisms [J].
Chen, L ;
Chetkovich, DM ;
Petralia, RS ;
Sweeney, NT ;
Kawasaki, Y ;
Wenthold, RJ ;
Bredt, DS ;
Nicoll, RA .
NATURE, 2000, 408 (6815) :936-943
[6]   DIFFERENTIAL REARING ALTERS SPINE DENSITY ON MEDIUM-SIZED SPINY NEURONS IN THE RAT CORPUS STRIATUM - EVIDENCE FOR ASSOCIATION OF MORPHOLOGICAL PLASTICITY WITH EARLY RESPONSE GENE-EXPRESSION [J].
COMERY, TA ;
SHAH, R ;
GREENOUGH, WT .
NEUROBIOLOGY OF LEARNING AND MEMORY, 1995, 63 (03) :217-219
[7]   Selective elimination of glutamatergic synapses on striatopallidal neurons in Parkinson disease models [J].
Day, M ;
Wang, ZF ;
Ding, J ;
An, XH ;
Ingham, CA ;
Shering, AF ;
Wokosin, D ;
Ilijic, E ;
Sun, ZX ;
Sampson, AR ;
Mugnaini, E ;
Deutch, AY ;
Sesack, SR ;
Arbuthnott, GW ;
Surmeier, DJ .
NATURE NEUROSCIENCE, 2006, 9 (02) :251-259
[8]  
El-Hussein AE, 2000, SCIENCE, V290, P1364
[9]   Separable features of visual cortical plasticity revealed by N-methyl-D-aspartate receptor 2A signaling [J].
Fagiolini, M ;
Katagiri, H ;
Miyamoto, H ;
Mori, H ;
Grant, SGN ;
Mishina, M ;
Hensch, TK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (05) :2854-2859
[10]  
Fiala JC, 1998, J NEUROSCI, V18, P8900