Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; University Center of Competence Sleep & Health Zurich (CRPP), University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland
Maurizio Scandella
Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
Sergio I Nemirovsky
Institute of Biological Chemistry, School of Exact and Natural Sciences (IQUIBICEN). CONICET – University of Buenos Aires, Buenos Aires, Argentina
Sven Leach
Child Development Center, University Children’s Hospital Zurich, University of Zurich, Zurich, Switzerland
Reto Huber
University Center of Competence Sleep & Health Zurich (CRPP), University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland; Child Development Center, University Children’s Hospital Zurich, University of Zurich, Zurich, Switzerland; Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zurich, Zurich, Switzerland
Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland; University Center of Competence Sleep & Health Zurich (CRPP), University of Zurich, Zurich, Switzerland; Neuroscience Center Zurich (ZNZ), Zurich, Switzerland
Slow waves and cognitive output have been modulated in humans by phase-targeted auditory stimulation. However, to advance its technical development and further our understanding, implementation of the method in animal models is indispensable. Here, we report the successful employment of slow waves’ phase-targeted closed-loop auditory stimulation (CLAS) in rats. To validate this new tool both conceptually and functionally, we tested the effects of up- and down-phase CLAS on proportions and spectral characteristics of sleep, and on learning performance in the single-pellet reaching task, respectively. Without affecting 24 hr sleep-wake behavior, CLAS specifically altered delta (slow waves) and sigma (sleep spindles) power persistently over chronic periods of stimulation. While up-phase CLAS does not elicit a significant change in behavioral performance, down-phase CLAS exerted a detrimental effect on overall engagement and success rate in the behavioral test. Overall CLAS-dependent spectral changes were positively correlated with learning performance. Altogether, our results provide proof-of-principle evidence that phase-targeted CLAS of slow waves in rodents is efficient, safe, and stable over chronic experimental periods, enabling the use of this high-specificity tool for basic and preclinical translational sleep research.
