Sleep spindles mediate hippocampal-neocortical coupling during sharp-wave ripples

Abstract

Sleep is pivotal for the consolidation of memories [1]. According to two-stage accounts, experiences are temporarily stored in the hippocampus and gradually translocated to neocortical sites during nonrapid-eye-movement (NREM) sleep [2,3]. Mechanistically, information transfer is thought to rely on interactions between thalamocortical spindles and hippocampal ripples. In particular, spindles may open precisely-timed communication channels, across which reactivation patterns may travel between the hippocampus and cortical target sites when ripples occur. To test this hypothesis, we first derived time-frequency representations (TFRs) in hippocampus (HIPP) and at scalp electrode Cz (neocortex, NC) time-locked to individual hippocampal ripple events. Compared to matched ripplefree intervals, results revealed a concurrent increase in spindle power both in HIPP and NC. As revealed by coherence analysis, hippocampal-neocortical coupling was indeed enhanced in the spindle band around ripples. Finally, we examined the directionality of spindle coupling and observed a strong driving effect from NC to HIPP. Specifically, ~250 ms prior to the HIPP ripple, NC spindles emerge and entrain HIPP spindles. Both regions then remain synchronised until ~500 ms after the ripple.Consistent with recent rodent work, these findings suggest that active consolidation is initiated by neocortex and draws on neocortical-hippocampal-neocortical reactivation loops [4], with a role of sleep spindles in mediating this process.

Sharp wave-ripples in human amygdala and their coordination with hippocampus during NREM sleep

“…1CD). These findings extend observations of spindle synchrony between HPC and NC (14,16,29), or within NC (30), involving AMY in a widespread network of spindle-related coordination. Moreover, we observed several instances in which ripples were associated with locally enhanced spindle activity in both AMY and HPC.…”

“…1C) and phase synchrony ( Fig. 1D) signaled robust communication in the SPW (2-6 Hz) and spindle (12)(13)(14)(15)(16) Hz) ranges, indicating that activity in these frequency bands both co-occurs and is phase-locked between these brain sites. Importantly, amplitude correlations also peaked in the 50-100 Hz range comprising the ripple band (arrow), suggesting that ripples tend to co-occur between these structures, though with variable phase relations as evident from the lack of phase synchrony.…”

“…Importantly, the aforementioned AMY-HPC replay underlying emotional memory consolidation similarly coincides with HPC SPW-ripples (6), pointing to a key role for ripples in the AMY-HPC dialog. Of note, ripple-like activity has been described in animal AMY (19,20), raising the possibility of coordinated ripples between these brain structures, but, importantly, ripples have never been described in human AMY.Beside their close association with SPWs, HPC ripples are nested within HPC and NC ~13 Hz sleep spindles and ~1 Hz slow oscillations (SOs) (8, 21), enhancing HPC-NC information exchange and consolidation (16,22,23). Whether these additional oscillatory rhythms have a role to play in AMY-HPC communication, either on their own or in conjunction with ripples, also remains unexplored.…”

“…Beside their close association with SPWs, HPC ripples are nested within HPC and NC ~13 Hz sleep spindles and ~1 Hz slow oscillations (SOs) (8, 21), enhancing HPC-NC information exchange and consolidation (16,22,23). Whether these additional oscillatory rhythms have a role to play in AMY-HPC communication, either on their own or in conjunction with ripples, also remains unexplored.…”

The human thalamus orchestrates neocortical oscillations during NREM sleep

“…While our current data remain agnostic with regards to hippocampal activity, it has been shown in a single patient study, that hippocampal spindles are aligned with SOs in the ANT 74 . Hence, ANT related oscillations might not only migrate to the neocortex but likewise to the hippocampus, where spindles are known to govern ripples and associated memory reactivation 66,75 .Taken together, ANT related activity might critically contribute to the triple coupling of sleep oscillations and thus, the memory function of sleep. Future work will need to capture the association of ANTneocortical interactions with the behavioral expressions of memory consolidation, as well as continue characterizing the functionally diverse human thalamus.…”