Separability of calcium slow waves and functional connectivity during wake, sleep, and anesthesia

Abstract

Modulation of brain state, e.g., by anesthesia, alters the correlation structure of spontaneous activity, especially in the delta band. This effect has largely been attributed to the ∼1 Hz slow oscillation that is characteristic of anesthesia and nonrapid eye movement (NREM) sleep. However, the effect of the slow oscillation on correlation structures and the spectral content of spontaneous activity across brain states (including NREM) has not been comprehensively examined. Further, discrepancies between activity dynamics observed with hemoglobin versus calcium (GCaMP6) imaging have not been reconciled. Lastly, whether the slow oscillation replaces functional connectivity (FC) patterns typical of the alert state, or superimposes on them, remains unclear. Here, we use wide-field calcium imaging to study spontaneous cortical activity in awake, anesthetized, and naturally sleeping mice. We find modest brain state-dependent changes in infraslow correlations but larger changes in GCaMP6 delta correlations. Principal component analysis of GCaMP6 sleep/anesthesia data in the delta band revealed that the slow oscillation is largely confined to the first three components. Removal of these components revealed a correlation structure strikingly similar to that observed during wake. These results indicate that, during NREM sleep/anesthesia, the slow oscillation superimposes onto a canonical FC architecture.

Peripheral sensory stimulation elicits global slow waves by recruiting somatosensory cortex bilaterally

“…Future investigations may further our understanding of the state-dependence of sensory-evoked global waves in naturally sleeping animals, though it is practically challenging to evoke sensory stimulation while maintaining natural sleep. Though ketamine/xylazine anesthesia recapitulates many key features of natural sleep, anesthesia produces more homogenous, higher-amplitude SWs ( 41 ) and thus may represent a state in which SWs are enhanced beyond native physiology.…”

“…Individual data points represent individual mice. Sample size and specific time points were selected on the basis of previous studies examining network connectivity changes in mice ( 34 , 41 , 71 ). Prism 8 software was used to perform statistical testing.…”

Characterization of Developmental Changes in Spontaneous Electrical Activity of Medial Superior Olivary Neurons Before Hearing Onset With a Combination of Injectable and Volatile Anesthesia

“…Thus, the heterogeneity of inhibitory effects observed in the results of this study, may also be explained by the hypothesis that the physical and functional properties of the vasculature, the diffusive properties of the extracellular space between vessels and neurons, and the clearance mechanisms of extracellular fluid available during this developmental window may be important factors that determine the access of anesthetics to target neurons in the brain (Nicholson et al, 2000;Shi and Rodríguez-Contreras, 2016;Mestre et al, 2020). A major difference in the effects of ISO in adult animals compared to neonates is the induction of slow waves of neuronal activity, an effect not described in neonates (Golshani et al, 2009;Brier et al, 2019). In this study, we observed that a group of recorded cells were inactive.…”

An open source statistical and data processing toolbox for wide-field optical imaging in mice

“…Prior to imaging, typical surgical preparations were implemented 9,18 . Briefly, an optically transparent plexiglass window was implanted with translucent dental cement (C&B-Metabond, Parkell Inc., Edgewood, New York) following a midline incision and clearing of skin and periosteal membranes.…”

“…Therefore, there has been a transition to using wide-field optical imaging (WOI) techniques in the mouse, yielding similar blood-based surrogates of neural activity at a similar spatial scale 7 . The advent of genetically encoded calcium indicators (GECIs) enables cell-specific labelling and increased temporal resolution compared to traditionally measured hemodynamics [8][9][10] . Combined hemoglobin and fluorophore imaging is readily available with optical imaging systems and harnesses the advantages of GECIs as well as maintains a translatable blood-based recording directly comparable to human fMRI.…”