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Reviews in the Neurosciences

Editor-in-Chief: Huston, Joseph P.

Editorial Board Member: Topic, Bianca / Adeli, Hojjat / Buzsaki, Gyorgy / Crawley, Jacqueline / Crow, Tim / Eichenbaum, Howard / Gold, Paul / Holsboer, Florian / Korth, Carsten / Lubec, Gert / McEwen, Bruce / Pan, Weihong / Pletnikov, Mikhail / Robbins, Trevor / Schnitzler, Alfons / Stevens, Charles / Steward, Oswald / Trojanowski, John

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35% increased IMPACT FACTOR 2012: 3.260
Rank 104 out of 251 in category Neurosciences in the 2012 Thomson Reuters Journal Citation Report/Science Edition

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Hippocampal synaptic plasticity in Alzheimer’s disease: what have we learned so far from transgenic models?

Cristina Marchetti1 / 1, 2

1Laboratory of Molecular Mechanisms of Synaptic Plasticity, European Brain Research Institute, I-00143 Rome, Italy

2Institut de Pharmacologie Moléculaire et Cellulaire (IPMC), UMR6097 CNRS/UNSA, F-06560 Valbonne, France

Corresponding author

Citation Information: Reviews in the Neurosciences. Volume 22, Issue 4, Pages 373–402, ISSN (Online) 2191-0200, ISSN (Print) 0334-1763, DOI: 10.1515/rns.2011.035, July 2011

Publication History

Received:
2011-03-25
Accepted:
2011-04-15
Published Online:
2011-07-06

Abstract

Transgenic (Tg) mouse models of Alzheimer’s disease (AD) are used to investigate mechanisms underlying disease pathology and identify therapeutic strategies. Most Tg AD models, which at least partly recapitulate the AD phenotype, are based on insertion of one or more human mutations (identified in Familial AD) into the mouse genome, with the notable exception of the anti-NGF mouse, which is based on the cholinergic unbalance hypothesis. It has recently emerged that impaired hippocampal synaptic function is an early detectable pathological alteration, well before the advanced stage of amyloid plaque accumulation and general cell death. Nevertheless, electrophysiological studies performed on different Tg models or on the same model by different research groups have yielded contrasting results. We therefore summarized data from original research papers studying hippocampal synaptic function using electrophysiology, to review what we have learned so far. We analyzed results obtained using the following Tg models: (1) single/multiple APP mutations; (2) single presenilin (PS) mutations; (3) APPxPS1 mutations; (4) APPxPS1xtau mutations (3xTg); and (5) anti-NGF expressing (AD11) mice. We observed that the majority of papers focus on excitatory basic transmission and long-term potentiation, while few studies evaluate inhibitory transmission and long-term depression. We searched for common synaptic alterations in the various models that might underlie the memory deficits observed in these mice. We also considered experimental variables that could explain differences in the reported results and briefly discuss successful rescue strategies. These analyses should prove useful for future design of electrophysiology experiments to assess hippocampal function in AD mouse models.

Keywords: Alzheimer’s disease; hippocampus; synaptic plasticity; transgenic mouse

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