Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease

被引：849
作者：
Busche, Marc Aurel [1 ,4 ]
Eichhoff, Gerhard [1 ,4 ]
Adelsberger, Helmuth [1 ,4 ]
Abramowski, Dorothee [2 ]
Wiederhold, Karl-Heinz [2 ]
Haass, Christian [3 ,4 ]
Staufenbiel, Matthias [2 ]
Konnerth, Arthur [1 ,4 ]
Garaschuk, Olga [1 ,4 ]
机构：
[1] Tech Univ Munich, Inst Neurowissensch, D-80802 Munich, Germany
[2] Novartis Inst Biomed Res, CH-4002 Basel, Switzerland
[3] Univ Munich, Dept Biochem, Lab Neurodegenerat Dis Res, Adolf Butenandt Inst, D-80336 Munich, Germany
[4] Ctr Integrated Prot Sci, D-81377 Munich, Germany
来源：
SCIENCE | 2008年 / 321卷 / 5896期
关键词：
D O I：
10.1126/science.1162844
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
The neurodegeneration observed in Alzheimer's disease has been associated with synaptic dismantling and progressive decrease in neuronal activity. We tested this hypothesis in vivo by using two- photon Ca(2+) imaging in a mouse model of Alzheimer's disease. Although a decrease in neuronal activity was seen in 29% of layer 2/3 cortical neurons, 21% of neurons displayed an unexpected increase in the frequency of spontaneous Ca(2+) transients. These "hyperactive" neurons were found exclusively near the plaques of amyloid beta-depositing mice. The hyperactivity appeared to be due to a relative decrease in synaptic inhibition. Thus, we suggest that a redistribution of synaptic drive between silent and hyperactive neurons, rather than an overall decrease in synaptic activity, provides a mechanism for the disturbed cortical function in Alzheimer's disease.
引用
收藏
页码：1686 / 1689
页数：4
相关论文
共 40 条
[1]   Incidence and predictors of seizures in patients with Alzheimer's disease [J].
Amatniek, JC ;
Hauser, WA ;
DelCastillo-Castaneda, C ;
Jacobs, DM ;
Marder, K ;
Bell, K ;
Albert, M ;
Brandt, J ;
Stern, Y .
EPILEPSIA, 2006, 47 (05) :867-872
[2]   Stimulus dependence of two-state fluctuations of membrane potential in cat visual cortex [J].
Anderson, J ;
Lampl, I ;
Reichova, I ;
Carandini, M ;
Ferster, D .
NATURE NEUROSCIENCE, 2000, 3 (06) :617-621
[3]   Dynamics of ongoing activity: Explanation of the large variability in evoked cortical responses [J].
Arieli, A ;
Sterkin, A ;
Grinvald, A ;
Aertsen, A .
SCIENCE, 1996, 273 (5283) :1868-1871
[4]   Excitotoxic hippocampal lesions disrupt allocentric spatial learning in mice: effects of strain and task demands [J].
Arns, M ;
Sauvage, M ;
Steckler, T .
BEHAVIOURAL BRAIN RESEARCH, 1999, 106 (1-2) :151-164
[5]   AMPA receptor downscaling at the onset of Alzheimer's disease pathology in double knockin mice [J].
Chang, EH ;
Savage, MJ ;
Flood, DG ;
Thomas, JM ;
Levy, RB ;
Mahadomrongkul, V ;
Shirao, T ;
Aoki, C ;
Huerta, PT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (09) :3410-3415
[6]   Growth arrest of individual senile plaques in a model of Alzheimer's disease observed by in vivo multiphoton microscopy [J].
Christie, RH ;
Bacskai, BJ ;
Zipfel, WR ;
Williams, RM ;
Kajdasz, ST ;
Webb, WW ;
Hyman, BT .
JOURNAL OF NEUROSCIENCE, 2001, 21 (03) :858-864
[7]   A QUANTITATIVE MORPHOMETRIC ANALYSIS OF THE NEURONAL AND SYNAPTIC CONTENT OF THE FRONTAL AND TEMPORAL CORTEX IN PATIENTS WITH ALZHEIMERS-DISEASE [J].
DAVIES, CA ;
MANN, DMA ;
SUMPTER, PQ ;
YATES, PO .
JOURNAL OF THE NEUROLOGICAL SCIENCES, 1987, 78 (02) :151-164
[8]   In vivo calcium imaging of the aging and diseased brain [J].
Eichhoff, Gerhard ;
Busche, Marc Aurel ;
Garaschuk, Olga .
EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, 2008, 35 (Suppl 1) :S99-S106
[9]   Visualizing the cortical representation of whisker touch: Voltage-sensitive dye imaging in freely moving mice [J].
Ferezou, Isabelle ;
Bolea, Sonia ;
Petersen, Carl C. H. .
NEURON, 2006, 50 (04) :617-629
[10]   Targeted bulk-loading of fluorescent indicators for two-photon brain imaging in vivo [J].
Garaschuk, Olga ;
Milos, Ruxandra-Iulia ;
Konnerth, Arthur .
NATURE PROTOCOLS, 2006, 1 (01) :380-386
1234