Place cell firing correlates with memory deficits and amyloid plaque burden in Tg2576 Alzheimer mouse model

被引:112
作者
Cacucci, Francesca [1 ]
Yi, Ming [1 ]
Wills, Thomas J. [1 ]
Chapman, Paul [2 ]
O'Keefe, John [1 ]
机构
[1] UCL, Dept Anat & Dev Biol, London WC1E 6BT, England
[2] GlaxoSmithKline Ctr Cognit & Neurodegenerat Disor, Singapore 138667, Singapore
基金
英国惠康基金; 英国生物技术与生命科学研究理事会;
关键词
Alzheimer's disease; hippocampus; spatial memory;
D O I
10.1073/pnas.0802908105
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
Alzheimer's disease (AD) is associated with progressive memory decline. Hippocampal place cells are a well understood candidate for the neural basis of one type of memory in rodents; these cells identify the animal's location in an environment and are crucial for spatial memory and navigation. We have recorded place cells in the Tg2576 mouse model of AD, and we report that aged (16 mo) but not young (3 mo) transgenic mice show degraded neuronal representations of the environment. The level of place cell degradation correlates with the animals' (poorer) spatial memory as tested in a forced-choice spatial alternation T-maze task and with hippocampal, but not neocortical, amyloid plaque burden.. Place cell recording provides a sensitive assay for measuring the amount and rate of functional deterioration in animal models of dementia as well as providing a quantifiable physiological indication of the beneficial. effects of potential therapies.
引用
收藏
页码:7863 / 7868
页数:6
相关论文
共 30 条
[1]   NEUROFIBRILLARY TANGLES BUT NOT SENILE PLAQUES PARALLEL DURATION AND SEVERITY OF ALZHEIMERS-DISEASE [J].
ARRIAGADA, PV ;
GROWDON, JH ;
HEDLEYWHYTE, ET ;
HYMAN, BT .
NEUROLOGY, 1992, 42 (03) :631-639
[2]   Intramaze and extramaze cue processing in adult APPSWE Tg2576 transgenic mice [J].
Barnes, P ;
Hale, G ;
Good, M .
BEHAVIORAL NEUROSCIENCE, 2004, 118 (06) :1184-1195
[3]   Quantitative measurement of changes in amyloid-β(40) in the rat brain and cerebrospinal fluid following treatment with the γ-secretase inhibitor LY-411575 [N2-[(2S)-2-(3,5-difluorophenyl)-2-hydroxyethanoyl]-N1-[(7S)-5-methyl-6-oxo-6,7-dihydro-5H-dibenzo[b,d]azepin-7-yl]-L-alaninamide] [J].
Best, JD ;
Jay, MT ;
Otu, F ;
Ma, J ;
Nadin, A ;
Ellis, S ;
Lewis, HD ;
Pattison, C ;
Reilly, M ;
Harrison, T ;
Shearman, MS ;
Williamson, TL ;
Atack, JR .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2005, 313 (02) :902-908
[4]  
Braak H, 1998, J NEURAL TRANSM-SUPP, P97
[5]   Experience-dependent increase in CA1 place cell spatial information, but not spatial reproducibility, is dependent on the autophosphorylation of the α-isoform of the calcium/calmodulin-dependent protein kinase II [J].
Cacucci, Francesca ;
Wills, Thomas J. ;
Lever, Colin ;
Giese, Karl Peter ;
O'Keefe, John .
JOURNAL OF NEUROSCIENCE, 2007, 27 (29) :7854-7859
[6]   Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice [J].
Chapman, PF ;
White, GL ;
Jones, MW ;
Cooper-Blacketer, D ;
Marshall, VJ ;
Irizarry, M ;
Younkin, L ;
Good, MA ;
Bliss, TVP ;
Hyman, BT ;
Younkin, SG ;
Hsiao, KK .
NATURE NEUROSCIENCE, 1999, 2 (03) :271-276
[7]   A learning deficit related to age and β-amyloid plaques in a mouse model of Alzheimer's disease [J].
Chen, GQ ;
Chen, KS ;
Knox, J ;
Inglis, J ;
Bernard, A ;
Martin, SJ ;
Justice, A ;
McConlogue, L ;
Games, D ;
Freedman, SB ;
Morris, RGM .
NATURE, 2000, 408 (6815) :975-979
[8]   Effects of cytotoxic hippocampal lesions in mice on a cognitive test battery [J].
Deacon, RMJ ;
Bannerman, DM ;
Kirby, BP ;
Croucher, A ;
Rawlins, JNP .
BEHAVIOURAL BRAIN RESEARCH, 2002, 133 (01) :57-68
[9]   Spatial relationship between synapse loss and β-amyloid deposition in Tg2576 mice [J].
Dong, Hongxin ;
Martin, Maureen V. ;
Chambers, Shawn ;
Csernansky, John G. .
JOURNAL OF COMPARATIVE NEUROLOGY, 2007, 500 (02) :311-321
[10]   Correlation between cognitive deficits and Aβ deposits in transgenic APP+PS1 mice [J].
Gordon, MN ;
King, DL ;
Diamond, DM ;
Jantzen, PT ;
Boyett, KV ;
Hope, CE ;
Hatcher, JM ;
DiCarlo, G ;
Gottschall, WPE ;
Morgan, D ;
Arendash, GW .
NEUROBIOLOGY OF AGING, 2001, 22 (03) :377-385