Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation
Sci Rep. 2016-03-07; 6(1):
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1. Sci Rep. 2016 Mar 7;6:22728. doi: 10.1038/srep22728.
Soluble amyloid beta oligomers block the learning-induced increase in hippocampal sharp wave-ripple rate and impair spatial memory formation.
Nicole O(1)(2), Hadzibegovic S(1)(2), Gajda J(3), Bontempi B(1)(2), Bem T(3), Meyrand P(1)(2).
(1)Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, 33000 Bordeaux, France.
(2)CNRS, Institut des Maladies Neurodégénératives, UMR 5293, 33000 Bordeaux, France.
(3)Nalecz Institute of Biocybernetics and Biomedical Engineering, Polish Academy of Sciences, 02-109, Warsaw, Poland.
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.
PMID: 26947247 [Indexed for MEDLINE]