title: Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation.
abstract: Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. While in Alzheimer's disease, abnormal hippocampal oscillations have been reported, the functional contribution of SWRs to the typically observed spatial memory impairments remains unclear. These impairments have been related to degenerative synaptic changes produced by soluble amyloid beta oligomers (Aβos) which, surprisingly, seem to spare the SWR dynamics during routine behavior. To unravel a potential effect of Aβos on SWRs in cognitively-challenged animals, we submitted vehicle- and Aβo-injected mice to spatial recognition memory testing. While capable of forming short-term recognition memory, Aβ mice exhibited faster forgetting, suggesting successful encoding but an inability to adequately stabilize and/or retrieve previously acquired information. Without prior cognitive requirements, similar properties of SWRs were observed in both groups. In contrast, when cognitively challenged, the post-encoding and -recognition peaks in SWR occurrence observed in controls were abolished in Aβ mice, indicating impaired hippocampal processing of spatial information. These results point to a crucial involvement of SWRs in spatial memory formation and identify the Aβ-induced impairment in SWRs dynamics as a disruptive mechanism responsible for the spatial memory deficits associated with Alzheimer's disease.
authors.affiliation: Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 33000 Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Nicole
authors.affiliation: Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 33000 Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Senka
authors.initials: S
authors.lastname: Hadzibegovic
authors.affiliation: Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 02-109, Warsaw, Poland.
authors.forename: Judyta
authors.initials: J
authors.lastname: Gajda
authors.affiliation: Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 33000 Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bontempi
authors.affiliation: Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 02-109, Warsaw, Poland.
authors.forename: Tiaza
authors.initials: T
authors.lastname: Bem
authors.affiliation: Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 33000 Bordeaux, France.|CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Meyrand
mesh_terms: D000200:Action Potentials; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D007858:Learning; D008297:Male; D008810:Mice, Inbred C57BL; D065852:Spatial Memory
chemical_list: D016229:Amyloid beta-Peptides