Harnessing olfactory bulb oscillations to perform fully brain-based sleep-scoring and real-time monitoring of anaesthesia depth

PLoS Biol. 2018 Nov 8;16(11):e2005458. doi: 10.1371/journal.pbio.2005458. eCollection 2018 Nov.

Abstract

Real-time tracking of vigilance states related to both sleep or anaesthesia has been a goal for over a century. However, sleep scoring cannot currently be performed with brain signals alone, despite the deep neuromodulatory transformations that accompany sleep state changes. Therefore, at heart, the operational distinction between sleep and wake is that of immobility and movement, despite numerous situations in which this one-to-one mapping fails. Here we demonstrate, using local field potential (LFP) recordings in freely moving mice, that gamma (50-70 Hz) power in the olfactory bulb (OB) allows for clear classification of sleep and wake, thus providing a brain-based criterion to distinguish these two vigilance states without relying on motor activity. Coupled with hippocampal theta activity, it allows the elaboration of a sleep scoring algorithm that relies on brain activity alone. This method reaches over 90% homology with classical methods based on muscular activity (electromyography [EMG]) and video tracking. Moreover, contrary to EMG, OB gamma power allows correct discrimination between sleep and immobility in ambiguous situations such as fear-related freezing. We use the instantaneous power of hippocampal theta oscillation and OB gamma oscillation to construct a 2D phase space that is highly robust throughout time, across individual mice and mouse strains, and under classical drug treatment. Dynamic analysis of trajectories within this space yields a novel characterisation of sleep/wake transitions: whereas waking up is a fast and direct transition that can be modelled by a ballistic trajectory, falling asleep is best described as a stochastic and gradual state change. Finally, we demonstrate that OB oscillations also allow us to track other vigilance states. Non-REM (NREM) and rapid eye movement (REM) sleep can be distinguished with high accuracy based on beta (10-15 Hz) power. More importantly, we show that depth of anaesthesia can be tracked in real time using OB gamma power. Indeed, the gamma power predicts and anticipates the motor response to stimulation both in the steady state under constant anaesthetic and dynamically during the recovery period. Altogether, this methodology opens the avenue for multi-timescale characterisation of brain states and provides an unprecedented window onto levels of vigilance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Anesthesia / methods
  • Animals
  • Brain / physiology
  • Electroencephalography / methods
  • Electromyography
  • Hippocampus / physiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Olfactory Bulb / metabolism
  • Olfactory Bulb / physiology*
  • Sleep / drug effects
  • Sleep / physiology*
  • Sleep Stages / physiology
  • Sleep, REM / physiology
  • Wakefulness / physiology*

Associated data

  • Dryad/10.5061/dryad.8m6n5fs

Grants and funding

Ecole Normale Superieure for SB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Ministère de l’Enseignement Supérieur et de la Recherche Scientifique for GL and MML. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Agence Nationale de la Recherche (grant number ANR-12-BSV4-0013-02 [AstroSleep], ANR-16-CE37-0001 [Cocode], ANR-10-LABX-54 MEMO LIFE, and ANR-11-IDEX-0001-02 PSL* Research University). for KB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Fondation pour la Recherche sur le Cerveau (grant number AP FRC 2016). for KB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. City of Paris (Grant Emergence 2014). for KB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Centre National de la Recherche Scientifique (ATIP-Avenir (2014)). for KB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Fondation pour la Recherche Médicale for SB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Université de Recherche Paris Sciences et Lettres for SB. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.