Gamma CV as a Marker of Circadian Disruption in C57BL/6J Mice: Correlating Neural Desynchrony with Locomotor, Thermal, and Sleep Dysrhythmia across a Spectrum of Circadian Rhythms Disruption paradigms.

Abstract

2)BackgroundCircadian rhythm desynchrony (CD) occurs when there is a mismatch between the circadian clock and local time, such as shift work. Mouse models are commonly employed to study CD, but may have significant shortcomings such as environmental masking, a focus only on sleep physiology, and significant variability between study designs. ObjectiveThis study used in vivo telemetry for simultaneous, real-time monitoring of locomotor activity (LA), core body temperature (CBT), and brain activity (EEG) in freely moving C57BL/6J mice to assess CD effects. MethodsFour-month-old C57BL/6J mice (n=11) were surgically implanted with telemeters enabling simultaneous real-time recording of LA, CBT, EEG.: Mice were sequentially exposed to a control condition standard 12:12h light-dark cycle (T24) then 4, 8-day CD paradigms: 10:10 h short day (T20), social jet lag (SJL), repeated 6h phase advances (6A2), and a 3:3 h ultradian cycle (T6)For each paradigm, the final 48h of data (250 Hz) were analyzed. ResultsWe found clear differences in the severity of the effects of each CD paradigm on sleep and circadian fitness, where T20[~]T6>SJL>6A2. CBT revealed broader disruption, but EEG outputs proved the most sensitive indicators of internal desynchrony. ConclusionsEach CD paradigm produced a unique profile across behavioral, physiological, and neural domains. We have also identified Gamma CV as a novel, sensitive metric of CD. These results highlight the necessity of multimodal monitoring to accurately characterize the impact of ecologically relevant stressors on circadian and sleep physiology. Statement of SignificanceCircadian rhythm desynchrony (CD), driven by shift work, jet lag, and modern irregular light exposure, is a major health burden linked to metabolic, neurodegenerative, and neuropsychiatric diseases. However, standard methods for measuring CD in laboratory models often rely on simple locomotor activity, which can "mask" the true extent of internal circadian stress. In this study, we simultaneously monitored brain EEG activity, core body temperature, and motion across four distinct models of circadian stress. We discovered that locomotor activity is a deceptive indicator of health; while mice appeared to show no alterations under several stress paradigms, their brain waves and body temperatures revealed the underlying impact of CD. Specifically, we identified "Gamma CV" as a highly sensitive new brain-wave marker that detects early circuit instability even when behavior appears normal and sleep quantity is preserved. These findings provide a marker for identifying early neurological vulnerability to irregular light schedules, offering a potential bridge to understanding similar gamma brain-wave alterations seen in addiction, early-stage Alzheimers disease, and other disorders.