Search bioRxiv⌕ Search

Biology subjects

Gonzales, J. A.

Publications and source records attributed to Gonzales, J. A..

2 recordsLinked to original sources

Genuinely Blind Identification of Sleep Spindles through Trispectral Modulation Analysis

Sleep spindles, transient 11-16 Hz oscillatory bursts, are a defining electrographic feature of non-rem (NREM) sleep and a key biomarker of sleep physiology. A need for efficient and reliable identification of spindles motivates a large literature on automated detection algorithms. In this literature, annotation by trained sleep specialists remains the gold standard against which automated methods are trained, tuned and evaluated. However, inter-scorer agreement among experts is modest, which leaves a significant role for subjective judgment in the definition of a spindle. Finding objective, scorer-independent, criteria for identifying spindles remains an unresolved challenge. We report here a robust, highly specific, and previously unrecognized signature of spindle activity in the fourth-order spectrum (trispectrum), from which we identify the presence of spindles, characterize their waveforms, and obtain an optimal detection filter through a decomposition of the trispectrum (HOSD). Although it is a strictly blind, data-driven method, HOSD-based spindle identification and detection agrees well with expert annotation (median AUROC ~0.9), yet identifies many more events at the native threshold than both human scorers and comparison detectors. Many of these additional detections are confirmed as meeting AASM spindle criteria by four blinded specialists, demonstrating that spindle-like oscillatory bursting is prevalent below conventional human and automated detection thresholds. We observe that N2 sleep is distinguished principally by high-amplitude bursts, while low-amplitude bursting persists throughout NREM sleep, being globally suppressed only in REM sleep. We also describe robust identification of recording-specific spindle waveform properties such as frequency deceleration.

neuroscience↗

Early life adversity promotes gastrointestinal dysfunction through a sex-dependent phenotypic switch in enteric glia

Irritable bowel syndrome and related disorders of gut-brain interaction (DGBI) are common and exhibit a complex, poorly understood etiology that manifests as abnormal gut motility and pain. Risk factors such as biological sex, stressors during critical periods, and inflammation are thought to influence DGBI vulnerability by reprogramming gut-brain circuits, but the specific cells affected are unclear. Here, we used a model of early life stress to understand cellular mechanisms in the gut that produce DGBIs. Our findings identify enteric glia as a key cellular substrate in which stress and biological sex converge to dictate DGBI susceptibility. Enteric glia exhibit sexual dimorphism in genes and functions related to cellular communication, inflammation, and disease susceptibility. Experiencing early life stress has sex-specific effects on enteric glia that cause a phenotypic switch in male glia toward a phenotype normally observed in females. This phenotypic transformation is followed by physiological changes in the gut, mirroring those observed in DGBI in humans. These effects are mediated, in part, by alterations to glial prostaglandin and endocannabinoid signaling. Together, these data identify enteric glia as a cellular integration site through which DGBI risk factors produce changes in gut physiology and suggest that manipulating glial signaling may represent an attractive target for sex-specific therapeutic strategies in DGBIs.

physiology↗