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.
Highlights
Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation
We identified two peaks in hippocampal SWR occurrence during the 40 min following either the encoding or the recognition phases, a neuronal signature similar to that reported in associative spatial memory tasks in the rat[5,18]
This differential pattern may be due to the fact that in our recognition memory paradigm, mice were exposed only once to the maze prior to engaging into slow wave sleep (SWS) when ripples were recorded whereas in the previous work, animals were subjected to intensive multiple training sessions in which they had to extract specific learning rules
Summary
Post-learning hippocampal sharp wave-ripples (SWRs) generated during slow wave sleep are thought to play a crucial role in memory formation. 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. Upon occurrence of SWRs, ensembles of hippocampal place cells can replay in faster timescales their sequential activity triggered during a previous learning episode, suggesting an essential role for SWRs in driving memory consolidation processes and subsequent long-term stabilization of newly acquired spatial memory traces[6] When such SWRs are experimentally disrupted, it causes memory deficits in hippocampus-dependent memory tasks[7], further suggesting that abnormal hippocampal rhythmic activity can interfere with hippocampal information processing, a dysfunctional pattern observed in pathological conditions such as Alzheimer’s disease[8] (AD). We determined the signature of this Aβ o treatment on hippocampal SWRs in mice without cognitive requirements or while undergoing a single spatial discrimination session
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