Single closed‐loop acoustic stimulation targeting memory consolidation suppressed hippocampal ripple and thalamo‐cortical spindle activity in mice

Abstract

Brain rhythms of sleep reflect neuronal activity underlying sleep‐associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed‐loop acoustic stimulation in humans targeted to the SO Up‐state successfully enhanced the slow oscillation rhythm and phase‐dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation‐induced hippocampo‐thalamo‐cortical activity and retention performance on a hippocampus‐dependent object‐place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3‐h retention interval at the beginning of the light phase closed‐loop stimulation failed to improve retention significantly over sham. However, retention during SO Up‐state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second‐long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo‐cortical spindle activity. Importantly, dynamics of SO‐coupled hippocampal ripple activity distinguished SOUp‐state stimulation. Non‐rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed‐loop acoustic stimulation in mice to investigate the inter‐regional mechanisms underlying memory consolidation.

Possible mechanisms to improve sleep spindles via closed loop stimulation during slow wave sleep: A computational study

“…Closed-loop acoustic stimulation (CLAS), i.e., acoustic stimulation applied during a specific phase of the SO, presents an intriguing method to study network and behavioral responsiveness in a phase-dependent manner, even across species. CLAS is able to modify endogenous slow oscillations, sleep spindles, and hippocampal sharp-wave ripple activity [25][26][27][28][29][30] and has been shown to enhance sleep-associated memory consolidation [25,29,31]. For the response to CLAS brain state and timing (e.g., stimulation phase of the oscillatory rhythm) have proven decisive [28,30,32].…”

“…CLAS is able to modify endogenous slow oscillations, sleep spindles, and hippocampal sharp-wave ripple activity [25][26][27][28][29][30] and has been shown to enhance sleep-associated memory consolidation [25,29,31]. For the response to CLAS brain state and timing (e.g., stimulation phase of the oscillatory rhythm) have proven decisive [28,30,32]. CLAS is often used as a double stimulation with two stimuli given at the same phase of two successive SOs.…”

Editorial for the special issue: ‘Local to large‐scale networks in the sleeping brain’

“…Coordination of sleep oscillations can be triggered by sensory stimuli such as sounds, and can promote the consolidation of memories. Although the mechanisms remain unclear, Marshall et al provide evidence that such stimuli alter hippocampal sharp wave‐ripples as well as spindles in mice (Aksamaz et al, 2023). This emphasizes the need to better understand the difference between spontaneously‐ or sensory‐generated oscillations and their contribution to brain plasticity.…”