Orchestrated experience-driven Arc responses are disrupted in a mouse model of Alzheimer's disease

被引：85

作者：

Rudinskiy, Nikita ^{[1
]}

Hawkes, Jonathan M. ^{[1
,2
]}

Betensky, Rebecca A. ^{[3
]}

Eguchi, Megumi ^{[4
]}

Yamaguchi, Shun ^{[4
]}

Spires-Jones, Tara L. ^{[1
]}

Hyman, Bradley T. ^{[1
]}

机构：

[1] Harvard Univ, Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Alzheimers Dis Res Lab,Dept Neurol,Sch Med, Charlestown, MA USA

[2] Northeastern Univ, Behav Neurosci Program, Boston, MA 02115 USA

[3] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

[4] Gifu Univ, Grad Sch Med, Div Morphol Neurosci, Gifu, Japan

来源：

NATURE NEUROSCIENCE | 2012年 / 15卷 / 10期

基金：

瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

LONG-TERM POTENTIATION; AMYLOID-BETA; SYNAPTIC PLASTICITY; IN-VIVO; NEURONAL DYSFUNCTION; PROTEIN EXPRESSION; TRANSGENIC MICE; A-BETA; ARC/ARG3.1; PLAQUES;

D O I：

10.1038/nn.3199

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Experience-induced expression of immediate-early gene Arc (also known as Arg3.1) is known to be important for consolidation of memory. Using in vivo longitudinal multiphoton imaging, we found orchestrated activity-dependent expression of Arc in the mouse extrastriate visual cortex in response to a structured visual stimulation. In wild-type mice, the amplitude of the Arc response in individual neurons strongly predicted the probability of reactivation by a subsequent presentation of the same stimulus. In a mouse model of Alzheimer's disease, this association was markedly disrupted in the cortex, specifically near senile plaques. Neurons in the vicinity of plaques were less likely to respond, but, paradoxically, there were stronger responses in those few neurons around plaques that did respond. To the extent that the orchestrated pattern of Arc expression reflects nervous system responses to and physiological consolidation of behavioral experience, the disruption in Arc patterns reveals plaque-associated interference with neural network integration.

引用

页码：1422 / 1429

页数：8

共 51 条

[1] MODIFICATION OF VISUAL CORTEX BY EXPERIENCE [J].