Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats
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Curated by eLife
Evaluation Summary:
This manuscript describes their phase-targeted closed-loop auditory stimulation protocol to alter slow wave oscillations in rodents. This manuscript provides a set of proof-of-concept data for a rodent model of closed-loop auditory stimulation during sleep as a method for augmenting NREM sleep thalamocortical oscillations and its behavioral effect on a motor task. The strongest contribution of this study to the field is that it provides a technical basis for future studies to be carried out which actually explore the neurobiological underpinnings of CLAS in detail. Applying this tool to rodent research in future studies may allow for bridging some of the putative mechanisms underlying memory consolidation (e.g., replay during NREM sleep) and behavioral changes observed with sleep (e.g., improved hippocampus-dependent memory). It's also nice to have a non-invasive way to manipulate sleep, particularly to translate rodent research to clinical work.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Abstract
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.
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Evaluation Summary:
This manuscript describes their phase-targeted closed-loop auditory stimulation protocol to alter slow wave oscillations in rodents. This manuscript provides a set of proof-of-concept data for a rodent model of closed-loop auditory stimulation during sleep as a method for augmenting NREM sleep thalamocortical oscillations and its behavioral effect on a motor task. The strongest contribution of this study to the field is that it provides a technical basis for future studies to be carried out which actually explore the neurobiological underpinnings of CLAS in detail. Applying this tool to rodent research in future studies may allow for bridging some of the putative mechanisms underlying memory consolidation (e.g., replay during NREM sleep) and behavioral changes observed with sleep (e.g., improved hippocampus-dependent …
Evaluation Summary:
This manuscript describes their phase-targeted closed-loop auditory stimulation protocol to alter slow wave oscillations in rodents. This manuscript provides a set of proof-of-concept data for a rodent model of closed-loop auditory stimulation during sleep as a method for augmenting NREM sleep thalamocortical oscillations and its behavioral effect on a motor task. The strongest contribution of this study to the field is that it provides a technical basis for future studies to be carried out which actually explore the neurobiological underpinnings of CLAS in detail. Applying this tool to rodent research in future studies may allow for bridging some of the putative mechanisms underlying memory consolidation (e.g., replay during NREM sleep) and behavioral changes observed with sleep (e.g., improved hippocampus-dependent memory). It's also nice to have a non-invasive way to manipulate sleep, particularly to translate rodent research to clinical work.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Reviewer #1 (Public Review):
This manuscript does a great job of describing their phase-targeted closed-loop auditory stimulation protocols to alter slow wave oscillations in rodents and alter behavior on a motor task. They are able to stimulate an auditory stimulus within ~5 degrees of the target, both during the ascending and descending (termed up-phase and down-phase). They showed that stimulating during the up-phase increased delta and sigma while stimulating the down-phase decreased delta and sigma. They also showed that stimulating the up-phase improved performance on a motor task while stimulating the down-phase generally decreased performance. There is translational value to this approach as this has been previously used in human subjects- altering slow wave oscillation to improve memory consolidation (a hot topic in …
Reviewer #1 (Public Review):
This manuscript does a great job of describing their phase-targeted closed-loop auditory stimulation protocols to alter slow wave oscillations in rodents and alter behavior on a motor task. They are able to stimulate an auditory stimulus within ~5 degrees of the target, both during the ascending and descending (termed up-phase and down-phase). They showed that stimulating during the up-phase increased delta and sigma while stimulating the down-phase decreased delta and sigma. They also showed that stimulating the up-phase improved performance on a motor task while stimulating the down-phase generally decreased performance. There is translational value to this approach as this has been previously used in human subjects- altering slow wave oscillation to improve memory consolidation (a hot topic in neuroscience). Applying this tool to rodent research in future studies may allow for bridging some of the putative mechanisms underlying memory consolidation (e.g., replay during NREM sleep) and behavioral changes observed with sleep (e.g., improved hippocampus-dependent memory). It's also nice to have a non-invasive way to manipulate sleep, particularly as we want to translate rodent research to clinical work.
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Reviewer #2 (Public Review):
Numerous recent studies with human subjects have suggested that periodic auditory stimuli, delivered at a particular phase with respect to NREM thalamocortical oscillations, have the capacity to promote memory consolidation during sleep. However, the underlying neurobiological mechanisms are less well understood. In order to characterize changes occurring within the thalamocortical circuitry during such closed-loop stimulation, the authors have carried out preliminary proof of principle work here in a rat model. In the model, closed-loop auditory stimulation (CLAS) is delivered across multiple days to rats, at different phases with respect to ongoing EEG rhythms. Effects of CLAS on EEG spectral power and performance on an multi-day motor learning paradigm have been assessed. The results largely replicate …
Reviewer #2 (Public Review):
Numerous recent studies with human subjects have suggested that periodic auditory stimuli, delivered at a particular phase with respect to NREM thalamocortical oscillations, have the capacity to promote memory consolidation during sleep. However, the underlying neurobiological mechanisms are less well understood. In order to characterize changes occurring within the thalamocortical circuitry during such closed-loop stimulation, the authors have carried out preliminary proof of principle work here in a rat model. In the model, closed-loop auditory stimulation (CLAS) is delivered across multiple days to rats, at different phases with respect to ongoing EEG rhythms. Effects of CLAS on EEG spectral power and performance on an multi-day motor learning paradigm have been assessed. The results largely replicate what has been found previously in CLAS studies with human subjects: upstate-targeted stimulation augments NREM thalamocortical oscillations. While upstate-targeted CLAS did not have any clear effect on motor learning, downstate-targeted CLAS appeared to reduce overall engagement with the motor task. While the present study does not provide additional information regarding neurobiological underpinnings of performance improvement driven by CLAS, the developed model has potential to do so in the future.
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