Ripple-triggered stimulation of the locus coeruleus during post-learning sleep disrupts ripple/spindle coupling and impairs memory consolidation

Abstract

Experience-induced replay of neuronal ensembles occurs during hippocampal high-frequency oscillations, or ripples. Post-learning increase in ripple rate is predictive of memory recall, while ripple disruption impairs learning. Ripples may thus present a fundamental component of a neurophysiological mechanism of memory consolidation. In addition to system-level local and cross-regional interactions, a consolidation mechanism involves stabilization of memory representations at the synaptic level. Synaptic plasticity within experience-activated neuronal networks is facilitated by noradrenaline release from the axon terminals of the locus coeruleus (LC). Here, to better understand interactions between the system and synaptic mechanisms underlying "off-line" consolidation, we examined the effects of ripple-associated LC activation on hippocampal and cortical activity and on spatial memory. Rats were trained on a radial maze; after each daily learning session neural activity was monitored for 1 h via implanted electrode arrays. Immediately following "on-line" detection of ripple, a brief train of electrical pulses (0.05 mA) was applied to LC. Low-frequency (20 Hz) stimulation had no effect on spatial learning, while higher-frequency (100 Hz) trains transiently blocked generation of ripple-associated cortical spindles and caused a reference memory deficit. Suppression of synchronous ripple/spindle events appears to interfere with hippocampal-cortical communication, thereby reducing the efficiency of "off-line" memory consolidation.