Single acoustic closed loop stimulation in mice to modulate hippocampo-thalamo-cortical activity and performance

Abstract

Neural brain rhythms of sleep reflect neuronal activity underlying sleep-associated memory consolidation. The modulation of brain rhythms, for instance the sleep slow oscillation (SO) is used both to investigate neurophysiological mechanisms as well as to measure the impact on presumed functional correlates. In humans, auditory closed-loop stimulation 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 task in mice. Closed-loop acoustic stimuli applied during four SO phases always acutely increased sharp wave ripple (SPWR) activity without disrupting non-rapid eye movement (NREM) sleep. Stimulation achieved an above chance preference index for stimuli delivered across a 3 h retention interval of sleep at the SO Up-state and at the Down-to-Up-state, but not at the Down-state nor late Up-state/Up-to Down-state. Results support the use of closed-loop acoustic stimulation in mice to investigate the inter-regional mechanisms underlying memory consolidation.