Biology subjects

Ehlen, J. C.

Publications and source records attributed to Ehlen, J. C..

6 recordsLinked to original sources

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

Environmental circadian disruption re-programs liver circadian gene expression

Circadian gene expression is fundamental to the establishment and functions of the circadian clock, a cell-autonomous and evolutionary-conserved timing system. Yet, how it is affected by environmental-circadian disruption (ECD) such as shiftwork and jetlag, which impact millions of people worldwide, are ill-defined. Here, we provided the first comprehensive description of liver circadian gene expression under normal and after ECD conditions. We found that post-transcription and post-translation processes are dominant contributors to whole-cell or nuclear circadian proteome, respectively. Furthermore, rhythmicity of 64% transcriptome, 98% whole-cell proteome and 95% nuclear proteome is re-written by ECD. The re-writing, which is associated with changes of circadian cis-regulatory elements, RNA-processing and protein trafficking, diminishes circadian regulation of fat and carbohydrate metabolism and persists after one week of ECD-recovery. One-Sentence SummaryEnvironmental-circadian disruption re-writes the circadian gene expression process which persists after one week of recovery.

molecular biology↗

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↗

bioRxiv2021

Arginine-Vasopressin Expressing Neurons in the Murine Suprachiasmatic Nucleus Exhibit a Circadian Rhythm in Network Coherence in vivo

The Suprachiasmatic Nucleus (SCN) is composed of functionally distinct sub-populations of GABAergic neurons which form a neural network responsible for synchronizing most physiological and behavioral circadian rhythms in mammals. To date, little is known regarding which aspects of SCN rhythmicity are generated by individual SCN neurons, and which aspects result from neuronal interaction within a network. Here, we utilize in vivo miniaturized microscopy to measure fluorescent GCaMP-reported calcium dynamics in AVP-expressing neurons in the intact SCN of awake, behaving mice. We report that SCN AVP neurons exhibit periodic, slow calcium waves which we demonstrate, using in vivo electrical recordings, likely reflect burst-firing. Further, we observe substantial heterogeneity of function in that AVP neurons exhibit unstable rhythms, and relatively weak rhythmicity at the population level. Network analysis reveals that correlated cellular behavior, or coherence, among neuron pairs also exhibited stochastic rhythms with about 33% of pairs rhythmic at any time. Unlike single-cell variables, coherence exhibited a strong rhythm at the population level with time of maximal coherence among AVP neuronal pairs at CT/ZT 6 and 9, coinciding with the timing of maximal neuronal activity for the SCN as a whole. These results demonstrate robust circadian variation in the coordination between stochastically rhythmic neurons and that interactions between AVP neurons in the SCN may be more influential than single-cell activity in the regulation of circadian rhythms. Furthermore, they demonstrate that cells in this circuit, like those in many other circuits imaged in vivo, exhibit profound heterogenicity of function over time and space. Significance StatementThis work is the first to employ two novel in vivo recording techniques, miniaturized calcium microscopy and optogentically-targeted single unit activity recording, to examine the rhythmic behavior of AVP expressing neurons both at the individual neuronal and network level. These results suggest that while AVP neurons are important for organismal rhythmicity, individual cellular rhythms are unstable and diverse. However, we observed correlated activity among these neurons which appears more reliably rhythmic, suggesting that emergent network properties of the SCN may be more relevant for organismal rhythmicity than individual neuronal characteristics.

neuroscience↗

bioRxiv2020

A novel female-specific circadian clock mechanism regulating metabolism

Circadian clocks enable organisms to predict and align their behaviors and physiologies to constant daily day-night environmental cycle. Because the ubiquitin ligase Siah2 has been identified as a potential regulator of circadian clock function in cultured cells, we have used Siah2-deficient mice to examine its function in vivo. Our experiments demonstrate a striking and unexpected sexually dimorphic effect of Siah2 deficiency on the regulation of rhythmically expressed genes. The absence of Siah2 in females, but not in males, altered the expression of core circadian clock genes and drastically remodeled the rhythmic hepatic transcriptome. Siah2 loss, only in females, increased the expression of 100s of genes selectively at mid-day, resulting in a >50% increase in the number of rhythmically expressed genes, and shifted the expression of 100s of other genes from a mid-night peak, to a mid-day peak. The combined result is a near inversion of overall rhythmicity in gene expression selectively in Siah2-deficient females. This dramatic reorganization created a substantial misalignment between rhythmic liver functions and feeding/behavioral rhythms, and consequently disrupted daily patterns of lipid/lipoprotein metabolism and metabolic responses to high-fat diet. Collectively, our results suggest that Siah2 is part of a female-specific circadian mechanism important for maintaining metabolic homeostasis and may play a key role in establishing sexual dimorphisms in metabolism, and broadly reveal that circadian clocks may drive rhythms using novel sex-specific transcriptional pathways.

physiology↗

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↗