Biology subjects

Paul, K. N.

Publications and source records attributed to Paul, K. N..

6 recordsLinked to original sources

bioRxiv2026

Bright Days Buffer Nighttime Light: Daytime Illumination Shapes Sex Differences in Sleep and Circadian Regulation

Sex differences in sleep and wakefulness are well documented in humans but remain inconsistent in rodent studies, suggesting strong sensitivity to experimental context. In prior work, we observed no sex differences in sleep-wake architecture under relatively bright daytime light, raising the possibility that daytime illumination is a critical but underappreciated variable shaping sex-dependent sleep regulation. Here, we tested the hypothesis that daytime light intensity modulates sex differences in sleep-wake architecture and vulnerability to dim light at night (DLaN). Male and female C57BL/6J mice were exposed to acute (one night) or chronic (two weeks) DLaN (10 lux) under three daytime light intensities (50, 100, 300 lux). Sleep was assessed using electroencephalographic-based measures of vigilance states and slow wave activity (SWA). Dim daytime light (50 lux) unmasked robust sex differences in dark-phase sleep-wake architecture that were absent under brighter daytime light (300 lux). Acute DLaN reduced early-night wakefulness in both sexes under low daytime light but had minimal effect under bright daytime conditions. Following chronic DLaN, males exhibited reduced dim light-phase wakefulness and dampened rhythm amplitude, whereas females showed pronounced phase shifts, rhythm attenuation, and altered timing of SWA under 50 and 100 lux. These changes were largely prevented under bright daytime light. Together, these findings identify daytime light intensity as a critical contextual factor governing sex-specific regulation of sleep and vulnerability to nighttime light, providing a unifying framework to reconcile inconsistencies in the rodent sleep literature. HighlightsO_LIDaytime light intensity shapes sex differences in sleep-wake architecture C_LIO_LIAcute and chronic nighttime light elicit distinct sex-specific sleep responses C_LIO_LIFemales exhibit greater circadian and slow-wave vulnerability to nighttime light C_LIO_LIBrighter daytime light buffers sleep and circadian disruption C_LI

animal behavior and cognition↗

bioRxiv2025

Dim Light at Night Disrupts the Sleep-Wake Cycle and Exacerbates Seizure Activity in Cntnap2 Knockout Mice: Implications for Autism Spectrum Disorders

Epilepsy is one of the most common comorbidities in individuals with autism spectrum disorders (ASDs). Many patients with epilepsy as well as ASD experience disruptions in their sleep-wake cycle and exhibit daily rhythms in expression of symptoms. Chronic exposure to light at nighttime can disrupt sleep and circadian rhythms. Contactin associated protein-like 2 knockout (Cntnap2 KO) mice, a model for autism spectrum disorder (ASD) and epilepsy, exhibit sleep and circadian disturbances and seizure-like events. This study examines how chronic dim light at night (DLaN) exposure affects sleep architecture, EEG power spectra, and seizure activity in Cntnap2 KO and wildtype (WT) mice. Using electroencephalography (EEG) recordings, male and female Cntnap2 KO and WT mice were exposed to DLaN (5 lux) for 2 or 6 weeks. EEG recordings were analyzed to assess sleep architecture, power spectrum, and seizure-like events. DLaN exposure delays the wake onset and disrupts sleep patterns in a sex-dependent manner, with females being more affected. DLaN significantly increased slow-wave activity (SWA, 0.5-4 Hz) in both WT and KO mice, indicating increased sleep pressure. Finally, we found that DLaN dramatically increased the frequency of seizure-like events in the Cntnap2 KO mice and even increased the occurrence rate in the WT mice. Spectral analysis of seizure-like events revealed increased theta power, suggesting the involvement of hippocampus. Chronic DLaN exposure disrupts sleep and increases seizure-like events in Cntnap2 KO mice, with sex-specific differences. These findings emphasize the potential risks of nighttime light exposure for individuals with ASD and epilepsy, reinforcing the need to manage light exposure to improve sleep quality and reduce seizure risk.

neuroscience↗

bioRxiv2024

Sleep patterns predicting stress resilience are dependent on sex

Sleep disturbances and stress have a well-established link with neuropsychiatric illness; however, the nature of this relationship remains unclear. Recently, studies using the mouse social-defeat stress model revealed a causal role for non-rapid eye movement (NREM) sleep in the maladaptive behavioral responses to stress. These results suggest a novel function for NREM sleep; as a response by cortical neurons to mitigate the maladaptive effects of stress. A major limitation in many social defeat studies has been the exclusion of females. Women exhibit a greater prevalence of both affective disorders and sleep disturbances compared to men, thus there is a clear need to understand sleep - stress interactions in females. The present study adapts recently developed female social-defeat stress models to allow social-defeat and EEG in male - female pairs. Our findings duplicate the behavioral responses that occur in other female, nondiscriminatory, and male models of social-defeat stress. Analysis of electroencephalographic (EEG) recordings, before exposure to stress, reveal that resilience is associated with differences in both NREM and REM sleep that are dependent on sex. After social defeat stress, NREM sleep was increased only in resilient males. In females, susceptibility to stress was associated with increased durations in NREM-sleep bouts. A potential cause of these sleep differences was also identified prior to stress exposure, sex differences in recovery from NREM-sleep loss; thus, suggesting an underlying sex-difference in the homeostatic process regulating sleep interactions with social-defeat stress. These findings suggest that NREM sleep quality is lower in resilient females, whereas the amount of REM sleep is decreased in susceptible females--when compared to males of the same behavioral phenotype. Overall, our findings reveal sexual dimorphism in both the sleep characteristics predicting resilience and sleep changes induced by social-defeat stress.

neuroscience↗

bioRxiv2023

Sex Differences in Sleep Phenotypes in the BACHD Mouse Model of Huntington's Disease

Sleep and circadian rhythm disturbances are common features of Huntingtons disease (HD). HD is an autosomal dominant neurodegenerative disorder that affects men and women in equal numbers, but some epidemiological studies as well as preclinical work indicate there may be sex differences in disease progression. Since sex differences in HD could provide important insights to understand cellular and molecular mechanism(s), we used the bacterial artificial chromosome transgenic mouse model of HD (BACHD) to examine whether sex differences in sleep/wake cycles are detectable in an animal model of the disease. Electroencephalography/electromyography (EEG/EMG) was used to measure sleep/wake states and polysomnographic patterns in young adult (12 week-old) male and female wild-type and BACHD mice. Our findings show that male, but not female, BACHD mice exhibited increased variation in phases of the rhythms as compared to age and sex matched wild-types. For both Rapid-eye movement (REM) and Non-rapid eye movement (NREM) sleep, genotypic and sex differences were detected. In particular, the BACHD males spent less time in NREM and exhibited a more fragmented sleep than the other groups. Both male and female BACHD mice exhibited significant changes in delta but not in gamma power compared to wild-type mice. Finally, in response to a 6-hrs sleep deprivation, both genotypes and sexes displayed predicted homeostatic responses to sleep loss. These findings suggest that females are relatively protected early in disease progression in this HD model. Significance StatementSleep and circadian rhythm disturbances are common features of Huntingtons disease (HD). Using an animal model of HD and EEG measures of sleep, we found that the males were more vulnerable to sleep/wake architecture alterations and sleep fragmentation. Homeostatic recovery from sleep loss did not appear to be altered at this stage of the disease. These findings raise the possibility that sex-specific factors play a role in the HD symptom progression and that hormone-based treatments may have therapeutic utility.

neuroscience↗

bioRxiv2022

Non-rapid eye movement sleep determines resilience to social stress

Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience. To examine if sleep has a determinative role in maladaptive behavioral-response to social stress, we investigated individual variations in resilience using a social-defeat model for male mice. Our results reveal a direct, causal relationship between sleep amount and resilience--demonstrating that sleep increases after social-defeat stress only occur in resilient mice. Further, we found that within the prefrontal cortex, a regulator of maladaptive responses to stress, pre-existing differences in sleep regulation predict resilience. Overall, these results demonstrate that increased NREM sleep, mediated cortically, is an active response to social-defeat stress that is both necessary and sufficient for promoting resilience. They also show that differences in resilience are strongly correlated with inter-individual variability in sleep regulation.

neuroscience↗

bioRxiv2020

Sleep Deprivation alters the influence of biological sex on active-phase sleep behavior

Poor sleep is a hazard of daily life that oftentimes cannot be avoided. Gender differences in daily sleep and wake patterns are widely reported; however, it remains unclear how biological sex, which is comprised of genetic and endocrine components, directly influences sleep regulatory processes. In the majority of model systems studied thus far, sex differences in daily sleep amount are predominant during the active (wake) phase of the sleep-wake cycle. The pervasiveness of sex differences in sleep amount throughout phylogeny suggests a strong underlying genetic component. The goal of the current study is to determine if sex differences in active-phase sleep amount are dependent on sex chromosomes in mice. Sleep was examined in the four-core genotype (FCG) mouse model, whose sex chromosome complement (XY, XX) is independent of sex phenotype (male or female). In this line, sex phenotype is determined by the presence or absence of the Sry gene, which is dissociated from the Y chromosome. Polysomnographic sleep recordings were obtained from gonadectomized (GDX) FCG mice to examine spontaneous sleep states and the ability to recover from sleep loss. We report that during the active-phase, the presence of the Sry gene accounts for most sex differences during spontaneous sleep; however, during recovery from sleep loss, sex differences in sleep amount are partially driven by sex chromosome complement. These results suggest that genetic factors on the sex chromosomes encode the homeostatic response to sleep loss.

neuroscience↗