A central role for the small GTPase Rac1 in hippocampal plasticity and spatial learning and memory

被引：114

作者：

Haditsch, Ursula ^{[1
]}

Leone, Dino P. ^{[2
]}

Farinelli, Melissa ^{[3
]}

Chrostek-Grashoff, Anna ^{[4
,5
]}

Brakebusch, Cord ^{[4
]}

Mansuy, Isabelle M. ^{[3
]}

McConnell, Susan K. ^{[2
]}

Palmer, Theo D. ^{[1
]}

机构：

[1] Stanford Sch Med, Dept Neurosurg, Stanford, CA 94305 USA

[2] Stanford Univ, Dept Biol, Stanford, CA 94305 USA

[3] Univ Zurich, Brain Res Inst, Zurich, Switzerland

[4] Univ Copenhagen, Biotech Res & Innovat Centre, Copenhagen, Denmark

[5] Univ Virginia Hlth Syst, Cardiovasc Res Ctr, Charlottesville, VA USA

来源：

MOLECULAR AND CELLULAR NEUROSCIENCE | 2009年 / 41卷 / 04期

关键词：

LONG-TERM POTENTIATION; DENDRITIC SPINE DEVELOPMENT; SIGNAL-REGULATED KINASE; NECROTIZING FACTOR-I; RHO-GTPASES; N-WASP; PROTEASOMAL DEGRADATION; ACTIN CYTOSKELETON; LIM-KINASE; ACTIVATION;

D O I：

10.1016/j.mcn.2009.04.005

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Rac1 is a member of the Rho family of small GTPases that are important for Structural aspects of the mature neuronal synapse including basal spine density and shape, activity-dependent spine enlargement, and AMPA receptor Clustering in vitro. Here we demonstrate that selective elimination of Rac1 in excitatory neurons in the forebrain in vivo not only affects spine structure, but also impairs synaptic plasticity in the hippocampus with consequent defects in hippocampus-dependent spatial learning. Furthermore, Rac1 mutants display deficits in working/episodic-like memory in the delayed matching-to-place (DMP) task Suggesting that Rac1 is a central regulator of rapid encoding of novel spatial information ill vivo. (c) 2009 Elsevier Inc. All rights reserved.

引用

页码：409 / 419

页数：11

共 61 条

[1] Regulation of hippocampal long-term potentiation by p21-activated protein kinase 1 (PAK1) [J].

Asrar, Suhail ;

Meng, Yanghong ;

Zhou, Zikai ;

Todorovski, Zarko ;

Huang, Wayne Wenyin ;

Jia, Zhengping .

NEUROPHARMACOLOGY, 2009, 56 (01) :73-80

[2] Proteins of the ADF/cofilin family: Essential regulators of actin dynamics [J].

Bamburg, JR .

ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 1999, 15 :185-230

[3] Biology of the p21-activated kinases [J].

Bokoch, GM .

ANNUAL REVIEW OF BIOCHEMISTRY, 2003, 72 :743-781

[4] Spine motility: Phenomenology, mechanisms, and function [J].

Bonhoeffer, T ;

Yuste, R .

NEURON, 2002, 35 (06) :1019-1027

[5] Development and regulation of dendritic spine synapses [J].

Calabrese, B ;

Wilson, MS ;

Halpain, S .

PHYSIOLOGY, 2006, 21 :38-47

[6] Rac1 is crucial for hair follicle integrity but is not essential for maintenance of the epidermis [J].

Chrostek, Anna ;

Wu, Xunwei ;

Quondamatteo, Fabio ;

Hu, Rong ;

Sanecka, Anna ;

Niemann, Catherin ;

Langbein, Lutz ;

Haase, Ingo ;

Brakebusch, Cord .

MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (18) :6957-6970

[7] THE SMALL GTP-BINDING PROTEINS RAC1 AND CDC42 REGULATE THE ACTIVITY OF THE JNK/SAPK SIGNALING PATHWAY [J].

COSO, OA ;

CHIARIELLO, M ;

YU, JC ;

TERAMOTO, H ;

CRESPO, P ;

XU, NG ;

MIKI, T ;

GUTKIND, JS .

CELL, 1995, 81 (07) :1137-1146

[8] The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo [J].

Davis, S ;

Vanhoutte, P ;

Pagés, C ;

Caboche, J ;

Laroche, S .

JOURNAL OF NEUROSCIENCE, 2000, 20 (12) :4563-4572

[9] Enhancement of learning and memory after activation of cerebral Rho GTPases [J].

Diana, Giovanni ;

Valentini, Giovanni ;

Travaglione, Sara ;

Falzano, Loreclana ;

Pieri, Massimo ;

Zona, Cristina ;

Meschini, Stefania ;

Fabbri, Alessia ;

Fiorentini, Carla .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (02) :636-641

[10] The actin cytoskeleton: Integrating form and function at the synapse [J].

Dillon, C ;

Goda, Y .

ANNUAL REVIEW OF NEUROSCIENCE, 2005, 28 :25-55

← 1 2 3 4 5 6 7 →