CA3 hippocampal synaptic plasticity supports ripple physiology during memory consolidation

Abstract

Consolidation of recent memory depends on hippocampal activities during resting periods that immediately follows the memory encoding. There, Slow Save Sleep phases appear as privileged periods for memory consolidation as hosting the ripple activities, which are fast oscillations generated within the hippocampus whose inactivation leads to memory impairment. If a strong correlation exists between these replays of recent experience and the persistence of behavioural adaptations, the mobilisation, the localization and the importance of synaptic plasticity events in this process is largely unknown. To question this issue, we used cell-surface AMPAR immobilisation to block post-synaptic LTP within the hippocampal region at various steps of the memory process. 1- Our results show that hippocampal synaptic plasticity is engaged during the consolidation but is dispensable during the encoding or recall of a working memory based spatial memory task. 2- Blockade of plasticity during sleep leads to apparent forgetting of the encoded rule. 3- In vivo recordings of ripple activities during resting periods show a strong impact of AMPAR immobilization solely, prominent when a rule has been recently encoded. 4- In situ examination of the interplay between AMPAR mobility, hippocampal plasticity and spontaneous ripple activities pointed that post-synaptic plasticity at CA3-CA3 recurrent synapses support ripple generation. As crucial results were reproduced using another AMPARM blockade strategy, we propose that after rule encoding, post-synaptic AMPAR mobility at CA3 recurrent synapses support the generation of ripples necessary for rule consolidation.

Neuronal FOS reports synchronized activity of presynaptic neurons

“…Replay of activity sequences during SWRs is important for memory consolidation ( 18 , 40 ). Synaptic potentiation occurs when pre-before-postsynaptic spike sequences are repeatedly combined with ripple-like subthreshold synaptic input ( 19 , 41 ).…”

“…We conclude that FOS is best triggered by synchronized glutamate release events repeating roughly every 10 seconds. In vivo, such high synchrony events (sharp-wave ripples) occur frequently during periods of quiet rest and slow-wave sleep and have been causally linked to memory consolidation ( 17 ) and long-term potentiation ( 18 , 19 ). We propose that FOS and its downstream proteins are specifically upregulated in neurons that repeatedly participate in ripple events, even if they fire only a single action potential per ripple.…”