A transgenic mouse model for Alzheimer's disease has impaired synaptic gain but normal synaptic dynamics

被引:4
作者
Ricoy, Ulises M. [1 ]
Mao, Peizhong [2 ]
Manczak, Maria [2 ]
Reddy, P. Hemachandra [2 ]
Frerking, Matthew E. [1 ]
机构
[1] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97239 USA
[2] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Beaverton, OR 97006 USA
关键词
Hippocampus; Synaptic; Glutamate; Alzheimer's; Amyloid; AMYLOID PRECURSOR PROTEIN; LONG-TERM POTENTIATION; HIPPOCAMPAL SYNAPSES; RELEASE PROBABILITY; A-BETA; MICE; TRANSMISSION; PLASTICITY; CORTEX; PRESENILIN-1;
D O I
10.1016/j.neulet.2011.06.043
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The chronic accumulation of amyloid beta (A beta) peptides is thought to underlie much of the pathology of Alzheimer's disease (AD), and transgenic mice overexpressing A beta show both behavioral defects and impairments in hippocampal synaptic transmission. In the present study, we examined excitatory transmission at the Schaffer collateral synapse in acute hippocampal slices from APP(Swe)/PS-1(A246E) transgenic mice to determine whether the synaptic impairment in these mice is due to a reduction in the activity-independent synaptic gain, or to a change in the activity-dependent synaptic dynamics. We observed a strong reduction in synaptic transmission in slices from APP(Swe)/PS-1(A246E) mice compared to those from their wildtype littermates. However, there was no resolvable change in the synaptic dynamics observed in response to either simple or complex stimulus trains. We conclude that the chronic accumulation of A beta impairs synaptic transmission through a reduction in the synaptic gain, while preserving the synaptic dynamics. (C) 2011 Published by Elsevier Ireland Ltd.
引用
收藏
页码:212 / 215
页数:4
相关论文
共 23 条
[1]   Amyloid-β as a positive endogenous regulator of release probability at hippocampal synapses [J].
Abramov, Efrat ;
Dolev, Iftach ;
Fogel, Hilla ;
Ciccotosto, Giuseppe D. ;
Ruff, Eyal ;
Slutsky, Inna .
NATURE NEUROSCIENCE, 2009, 12 (12) :1567-U120
[2]   Accelerated amyloid deposition in the brains of transgenic mice coexpressing mutant presenilin 1 and amyloid precursor proteins [J].
Borchelt, DR ;
Ratovitski, T ;
vanLare, J ;
Lee, MK ;
Gonzales, V ;
Jenkins, NA ;
Copeland, NG ;
Price, DL ;
Sisodia, SS .
NEURON, 1997, 19 (04) :939-945
[3]   Familial Alzheimer's disease-linked presenilin 1 variants elevate A beta 1-42/1-40 ratio in vitro and in vivo [J].
Borchelt, DR ;
Thinakaran, G ;
Eckman, CB ;
Lee, MK ;
Davenport, F ;
Ratovitsky, T ;
Prada, CM ;
Kim, G ;
Seekins, S ;
Yager, D ;
Slunt, HH ;
Wang, R ;
Seeger, M ;
Levey, AI ;
Gandy, SE ;
Copeland, NG ;
Jenkins, NA ;
Price, DL ;
Younkin, SG .
NEURON, 1996, 17 (05) :1005-1013
[4]   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
[5]   Response of hippocampal synapses to natural stimulation patterns [J].
Dobrunz, LE ;
Stevens, CF .
NEURON, 1999, 22 (01) :157-166
[6]   Age-related impairment of synaptic transmission but normal long-term potentiation in transgenic mice that overexpress the human APP695SWE mutant form of amyloid precursor protein [J].
Fitzjohn, SM ;
Morton, RA ;
Kuenzi, F ;
Rosahl, TW ;
Shearman, M ;
Lewis, H ;
Smith, D ;
Reynolds, DS ;
Davies, CH ;
Collingridge, GL ;
Seabrook, GR .
JOURNAL OF NEUROSCIENCE, 2001, 21 (13) :4691-4698
[7]   Spike timing in CA3 pyramidal cells during behavior:: Implications for synaptic transmission [J].
Frerking, M ;
Schulte, J ;
Wiebe, SP ;
Stäubli, U .
JOURNAL OF NEUROPHYSIOLOGY, 2005, 94 (02) :1528-1540
[8]   Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models [J].
Hsia, AY ;
Masliah, E ;
McConlogue, L ;
Yu, GQ ;
Tatsuno, G ;
Hu, K ;
Kholodenko, D ;
Malenka, RC ;
Nicoll, RA ;
Mucke, L .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (06) :3228-3233
[9]   AMPAR removal underlies Aβ-induced synaptic depression and dendritic spine loss [J].
Hsieh, Helen ;
Boehm, Jannic ;
Sato, Chihiro ;
Iwatsubo, Takeshi ;
Tomita, Taisuke ;
Sisodia, Sangram ;
Malinow, Roberto .
NEURON, 2006, 52 (05) :831-843
[10]   Alterations in synaptic transmission and long-term potentiation in hippocampal slices from young and aged PDAPP mice [J].
Larson, J ;
Lynch, G ;
Games, D ;
Seubert, P .
BRAIN RESEARCH, 1999, 840 (1-2) :23-35