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キーワード:
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要旨:
Sharp wave-ripple complexes are thought to play a major role in memory reactivation, transfer and consolidation. However, the large-scale cooperative mechanisms associated to these episodes and their relationship to the observed SPW-R electrical signature remains largely unknown. A better understanding of the underlying mechanisms of these interactions requires a finer characterization of the SPW-R phenomenon and its associated brain-wide signatures. To address this question, we hypothesize that SPW-R dynamics vary, reflecting distinct interactions with neocortical and subcortical systems depending on the state of the animal. Specifically, the wide-range network reconfiguration required by this process may bring different electrical signatures of SPW-Rs, thus reflecting different memory-related functional roles. Using concurrent hippocampal local field potentials (LFP) recordings and functional Magnetic Resonance Imaging (fMRI) in anesthetized macaques, we study local changes in neuronal activity during SPW-R episodes and their brain-wide correlates. After detecting SPW-R episodes based on power increases in the ripple frequency band (80-180 Hz), analysis of peri-event SPW-R complexes reveals four well-differentiated SPW-R subtypes in the CA1 LFP. Event-triggered fMRI maps show that SPW-R subtypes relate to differentiated multi-structure activity (MSA). We found that ripples aligned to the positive peak of their SPWs were associated with significantly higher BOLD up-regulations within the hippocampal formation, and in cortical associative areas (namely, anterior cingulate cortex, retrosplenial area, prefrontal, temporal and parietal cortices), as compared to ripples occurring at the trough of their SPW (p<0.01 Wilcoxon rank-sum test, FDR-corrected with q<0.05). Conversely, detailed analysis of all subcortical domains revealed differentiated BOLD activations in locus coeruleus (LC) and dorsal raphe nucleus (p<0.002, pairwise Wilcoxon rank-sum test, FDR-corrected with q<0.05), suggesting that emergence of different SPW-R signatures may be influenced by state-dependent neuromodulatory inputs of differentiated nature into the hippocampal formation. Altogether, our results suggest that the variability of CA1 SPW-R episodes reflect different levels of activation over cortical and subcortical domains. We hypothesize that these distinct patterns of SPW-R complexes reflect brain-wide cooperative events, possibly involved in different memory-related functions.
