Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in rats
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-h 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.
Data availability
The .edf files containing EEG/EMG signal (BL and M-T1-4), the corresponding labels detailing vigilance states (4s resolution), the temporal flags of the auditory triggers, and the counts from the single-pellet reaching task are publicly available in Dryad (doi:10.5061/dryad.bvq83bk99). All figures accompanied by an Excel file containing the numerical data and statistical analyses are provided with this submission as well as in the Dryad repository.
-
Closed-loop auditory stimulation method to modulate sleep slow waves and motor learning performance in ratsDryad Digital Repository, doi:10.5061/dryad.bvq83bk99.
Article and author information
Author details
Funding
Swiss National Science Foundation (163056 and 188790)
- Christian R Baumann
Synapsis Foundation for Alzheimer's Research
- Daniela Noain
Neuroscience Center Zurich, University of Zurich (Rahn and Bodmer donation)
- Daniela Noain
Armin and Jeannine Kurz Stiftung
- Daniela Noain
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Denise Cai, Icahn School of Medicine at Mount Sinai, United States
Ethics
Animal experimentation: All procedures were approved by the veterinary office of the Canton Zurich under license ZH231/2015.
Version history
- Received: March 4, 2021
- Preprint posted: March 18, 2021 (view preprint)
- Accepted: September 29, 2021
- Accepted Manuscript published: October 6, 2021 (version 1)
- Version of Record published: October 21, 2021 (version 2)
Copyright
© 2021, Moreira et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 2,200
- views
-
- 247
- downloads
-
- 14
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Further reading
-
- Neuroscience
Negative memories engage a brain and body-wide stress response in humans that can alter cognition and behavior. Prolonged stress responses induce maladaptive cellular, circuit, and systems-level changes that can lead to pathological brain states and corresponding disorders in which mood and memory are affected. However, it is unclear if repeated activation of cells processing negative memories induces similar phenotypes in mice. In this study, we used an activity-dependent tagging method to access neuronal ensembles and assess their molecular characteristics. Sequencing memory engrams in mice revealed that positive (male-to-female exposure) and negative (foot shock) cells upregulated genes linked to anti- and pro-inflammatory responses, respectively. To investigate the impact of persistent activation of negative engrams, we chemogenetically activated them in the ventral hippocampus over 3 months and conducted anxiety and memory-related tests. Negative engram activation increased anxiety behaviors in both 6- and 14-month-old mice, reduced spatial working memory in older mice, impaired fear extinction in younger mice, and heightened fear generalization in both age groups. Immunohistochemistry revealed changes in microglial and astrocytic structure and number in the hippocampus. In summary, repeated activation of negative memories induces lasting cellular and behavioral abnormalities in mice, offering insights into the negative effects of chronic negative thinking-like behaviors on human health.
-
- Neuroscience
Synaptic inputs to cortical neurons are highly structured in adult sensory systems, such that neighboring synapses along dendrites are activated by similar stimuli. This organization of synaptic inputs, called synaptic clustering, is required for high-fidelity signal processing, and clustered synapses can already be observed before eye opening. However, how clustered inputs emerge during development is unknown. Here, we employed concurrent in vivo whole-cell patch-clamp and dendritic calcium imaging to map spontaneous synaptic inputs to dendrites of layer 2/3 neurons in the mouse primary visual cortex during the second postnatal week until eye opening. We found that the number of functional synapses and the frequency of transmission events increase several fold during this developmental period. At the beginning of the second postnatal week, synapses assemble specifically in confined dendritic segments, whereas other segments are devoid of synapses. By the end of the second postnatal week, just before eye opening, dendrites are almost entirely covered by domains of co-active synapses. Finally, co-activity with their neighbor synapses correlates with synaptic stabilization and potentiation. Thus, clustered synapses form in distinct functional domains presumably to equip dendrites with computational modules for high-capacity sensory processing when the eyes open.