title: 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.
authors.affiliation: Max Planck Institute for Biological Cybernetics, Tubingen 72076, Germany.
authors.forename: Yulia
authors.initials: Y
authors.lastname: Novitskaya
authors.affiliation: Center for Integrative Research in Biology, CNRS-UMR7152, Collège de France, Paris 75005, France Department of Child and Adolescent Psychiatry, New York University Medical School, New York, New York 10016, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Sara
authors.affiliation: Max Planck Institute for Biological Cybernetics, Tubingen 72076, Germany Centre for Imaging Sciences, Biomedical Imaging Institute, University of Manchester, Manchester M13 9PT, United Kingdom.
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.affiliation: Max Planck Institute for Biological Cybernetics, Tubingen 72076, Germany oxana.eschenko@tuebingen.mpg.de.
authors.forename: Oxana
authors.initials: O
authors.lastname: Eschenko
mesh_terms: D000818:Animals; D001703:Biophysics; D003216:Conditioning, Operant / Q000502:physiology; D004558:Electric Stimulation; D004569:Electroencephalography; D005071:Evoked Potentials / Q000502:physiology; D006624:Hippocampus / Q000502:physiology; D008125:Locus Coeruleus / Q000502:physiology*; D008297:Male; D018782:Maze Learning; D000069077:Memory Consolidation / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology*; D011939:Mental Recall / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000502:physiology; D012890:Sleep / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D065852:Spatial Memory / Q000502:physiology; D018709:Statistics, Nonparametric