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The Journal of Neuroscience, August 1, 2001, 21(15):5703-5714
Generation of Aggregated  -Amyloid in the Rat Hippocampus
Impairs Synaptic Transmission and Plasticity and Causes Memory
Deficits
Aline
Stéphan,
Serge
Laroche, and
Sabrina
Davis
Laboratoire de Neurobiologie de l'Apprentissage, de la
Mémoire et de la Communication, Centre National de la Recherche
Scientifique Unité Mixte de Recherche 8620, Université Paris Sud, 91405 Orsay, France
We injected a combination of the  -amyloids (As) A40 and
A43 to "seed" formation of amyloid deposits in the dorsal
dentate gyrus of rats in vivo, on the basis of a theory
of Jarrett and Landsbury (1993). Rats were tested on several different
learning tasks, and synaptic transmission and plasticity were assessed in vivo. Between 7 and 16 weeks after injection, we
found aggregated amyloid material, reactive astrocytosis, microgliosis,
and cell loss around the sites of injection. Rats were impaired
specifically in working memory type tasks in accordance with the type
of memory deficit observed in the early stages of Alzheimer's disease.
Synaptic transmission and long-term potentiation, a candidate cellular mechanism for memory, were severely impaired in vivo.
Injections of the same dose of fragments individually did not induce
these effects. These findings suggest that aggregated amyloid material induces cognitive deficits similar to those observed in the early phases of Alzheimer's disease via an alteration in neuronal
transmission and plasticity.
Key words:
working memory; A40; A43; synaptic plasticity; Alzheimer's disease; dentate gyrus; senile plaque
Copyright © 2001 Society for Neuroscience 0270-6474/01/21155703-12$05.00/0
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