Biology subjects

Myung, J.

Publications and source records attributed to Myung, J..

10 recordsLinked to original sources

bioRxiv2026

A two-oscillator SCN model with period adaptation and systemic feedback captures photoperiod and T-cycle aftereffects in vivo and in explants

Light history leaves persistent changes in circadian period, but where this history is stored remains unresolved. Suprachiasmatic nucleus (SCN) network models have often approached photoperiodic encoding through phase organization or coupling strength. We computationally tested slow adaptation of subregion-specific intrinsic periods as an alternative memory mechanism. The model asymmetrically couples dorsal (D) and ventral (V) SCN oscillators and adds a systemic oscillator (X) representing putative circadian feedback present in vivo but lost ex vivo. With a single parameter set, period adaptation captured the direction and approximate magnitude of behavioral aftereffects across photoperiod and T-cycle conditions. Adapting coupling strength instead of period failed to reproduce the V-leading-D phase order reported after T22. Removing systemic feedback preserved the photoperiod-dependent period ordering but inverted the T22 and T26 aftereffects, an inversion that matched SCN explant observations. The model also yielded distinct D-V phase organization for each of 18:6 LD, T23, and T25. These results suggest that subregion-specific period plasticity provides a parsimonious substrate for encoding light history, while the dependence on systemic feedback indicates that behavioral period may not be a readout of the SCN alone. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/743784v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@d48266org.highwire.dtl.DTLVardef@1bd15bdorg.highwire.dtl.DTLVardef@de3d9forg.highwire.dtl.DTLVardef@9fbc39_HPS_FORMAT_FIGEXP M_FIG C_FIG A model with dorsal period adaptation and phenomenological systemic feedback accounts for behavioral and explanted SCN aftereffects. (A) During T22 entrainment, dorsal (D), ventral (V), and systemic (X) oscillators remain phase-locked. After release into constant darkness, systemic coupling maintains a unified in vivo rhythm, whereas removing X feedback in the explant simulation allows the D-V network to express a distinct ex vivo period aftereffect. (B) The SCN model is modeled as an asymmetrically coupled attractive-repulsive oscillator network with stronger photic input to V. Light history is encoded via plasticity of the intrinsic period in D, while X represents putative systemic circadian feedback available in vivo and lacking direct photic input. (C) The model reproduces concordant period changes in behavior and SCN explants across photoperiods, but opposing period changes following T-cycle entrainment.

neuroscience↗

bioRxiv2026

Chronotype asymmetry arises from stochastic sleep homeostasis under circadian entrainment

Study ObjectivesChronotype, typically defined by the mid-sleep phase on free days, is often interpreted as a direct proxy for circadian phase. However, a fundamental paradox challenges this assumption: worldwide chronotype distributions show a heavy right skew, whereas circadian period distributions show a slight left skew. We investigated whether fast, noisy cortical processes in homeostatic sleep pressure dynamics could resolve this paradox. MethodsDrawing upon the classical two-process model of sleep regulation, we simulated how interindividual differences in sleep homeostasis (Process S), combined with realistic circadian period distributions (Process C), interact to shape chronotype variability. We introduce stochasticity into sleep pressure build-up to test whether homeostatic variance generates the empirically observed right-skew in chronotype distributions. ResultsExploring the parameter space reveals that stable sleep-wake cycles are constrained within physiological limits of entrainment in an Arnold tongue-like structure. While our simulations confirm a general positive correlation between intrinsic period and chronotype, the heavy right tail of the chronotype distribution arises from interindividual variability in homeostatic sleep dynamics operating near the unstable boundaries of entrainment. This mechanism preserves the individual-level correlation but inverts the population-level skew from left to right. ConclusionsBehavioral chronotype emerges from the nonlinear interaction between fluctuating homeostatic sleep pressure and a hierarchically entrained circadian system. We caution against inferring the intrinsic circadian period solely from chronotype, particularly in clinical contexts where accurate assessment of circadian rhythmicity is critical for targeted therapies.

biophysics↗

bioRxiv2026

A multistable slow-fast model of affective state switching under circadian drive

Rhythmic mood fluctuations are often associated with circadian timing, but it remains unclear how daily rhythms that normally organize physiological affective variation also shape transitions into longer pathological episodes in bipolar disorder. We introduce a phenomenological slow-fast model of affective dynamics inspired by HPA-axis homeostatic feedback. A fast affective coordinate evolves on a multistable landscape whose geometry is shaped by a slow homeostatic variable, producing four stable wells: depression-like, physiological low, physiological high, and mania-like. Circadian input acts not as a local forcing term but as a periodic tilt of the global affective landscape. With intact barriers, this tilt entrains physiological low-high cycling; when outer barriers are weakened, it creates phase-dependent windows for stochastic escape into pathological wells, where prolonged occupancy can produce episode-like infradian cycling. Modeling persistent perturbations as an Ornstein-Uhlenbeck process, we derive a Kramers-type escape criterion linking pathological transitions to phase-dependent barrier height and perturbation strength. One-year simulations and scans over the parameter governing landscape geometry show that preserved circadian amplitude stabilizes physiological cycling, whereas reduced amplitude combined with stronger perturbations promotes entry into and occupancy within depression-like or mania-like wells. The model provides a dynamical framework for studying how circadian disruption, landscape geometry, and perturbation sensitivity jointly shape transitions between physiological mood cycling and episode-like pathological states. Lead ParagraphBipolar disorder involves large, persistent transitions among depressive, euthymic, and manic states, whereas everyday mood also shows smaller fluctuations over the day. Whether these two forms of affective variation can be understood within a single dynamical framework remains unclear. Here, we present a slow-fast affective landscape model in which a slow homeostatic variable shapes a multistable potential for a faster affective state. The landscape contains two inner physiological wells and two outer pathological wells. Circadian input does not force the affective state directly into particular wells; instead, it periodically tilts the global landscape, entraining daily cycling within the physiological low and high states under normal geometry. When circadian amplitude is weakened or outer barriers are reduced, persistent stochastic fluctuations can promote escape into hard-to-exit depression-like or mania-like states. The central issue is therefore not simply whether such escapes can occur, but how circadian disruption, landscape geometry, and perturbation sensitivity determine the balance of dwell time across physiological and pathological states over clinically meaningful observation windows.

biophysics↗

bioRxiv2025

Differential Effects of Sex and Age on Daily and Infradian Rhythms of Mice Running Title: Sex and Age Differences in Mouse Rhythms

Intrinsic biological rhythms regulate key physiological and behavioural processes, yet the influence of sex and age on these rhythms is not fully understood. We comprehensively examined 24-hour (circadian) and >24-hour (infradian; 5-day and 10-day) rhythms in wheel-running and ingestive behaviours in single-housed young and middle-aged male and female mice. Circadian analysis revealed that middle-aged mice, particularly females, exhibited more precise daily rhythms and shifted a greater proportion of activity and feeding to the lights-on phase compared to young female mice. Middle-aged animals also ran for longer durations per day, suggesting age-related changes in activity regulation. Analysis of infradian rhythms further highlighted sex- and age-specific differences. Young female mice displayed robust 5-day rhythms in wheel-running activity, which were absent in middle-aged females. In contrast, few males (young or middle-aged) showed significant 5-day rhythms. Ten-day rhythms were most prominent in male mice, while females rarely expressed this periodicity. Physiologically, middle-aged mice lost more body weight in response to single housing, with middle-aged females being most affected. Interactions among behavioural rhythms in females also showed greater complexity, which increased with age. These findings reveal distinct sex- and age-dependent patterns in circadian and infradian rhythms as well as in physiological responses to isolation. Our work highlights the need to account for sex and age in chronobiological research, with broader implications for understanding vulnerability to age-related metabolic and behavioural disorders.

animal behavior and cognition↗

bioRxiv2025

Choroid Plexus Hosts the Earliest Detectable Circadian Clock in the Brain

Maternal chronodisruption is linked to miscarriages and neurodevelopmental risks, yet the earliest brain circadian oscillator in the embryo and the mechanism of its emergence remain unknown. Using bioluminescent reporters for PER2 and Bmal1, we tracked the onset of autonomous [~]24 h oscillations ex vivo. While the suprachiasmatic nucleus (SCN) is widely considered the first circadian structure at embryonic day (E) 14.5-15.5, we find that the fourth ventricle choroid plexus (4VCP) exhibits PER2 oscillations by E11.5-E12.5. These oscillations show hallmarks of a saddle-node on an invariant circle (SNIC) bifurcation, characterized by an initially long period converging toward 24 h and pronounced sensitivity to sub-degree temperature cycles mimicking physiological maternal cues. Transcriptional profiling of maternal and embryonic 4VCPs unveiled three epochs in clock gene expression that parallel tissue differentiation. We identify the 4VCP as the earliest detectable brain circadian oscillator, and demonstrate how its bifurcation dynamics allow the nascent clock to couple to maternal rhythms.

developmental biology↗

bioRxiv2024

Selective enrichment of Methylococcaceae versus Methylocystaceae methanotrophs via control of methane feeding scheme

Methanotrophs are crucial in keeping environmental CH4 emissions in check. However, how different groups of methanotrophs contribute to this important role in different environmental settings remain ambiguous. Here, in a simplified laboratory setting of well-mixed batch reactors fed continuous flow of CH4-containing gas, methanotrophic microbiomes were enriched from paddy soils under six different incubation conditions prepared as combinations of two different CH4 mixing ratios (0.5% and 10% v/v) and three supplemented Cu2+ concentrations (0, 2, and 10 M). Monitoring of the temporal community shifts in the reactor microbiomes observed domination of Methylocystis spp. in all three reactors fed 0.5% v/v, as further supported by the analyses of pmoCAB genes in the shotgun metagenomes of the single-point samples from the same reactors. Copper deficiency did not select for mmoXYZ-possessing methanotrophs. Instead, a cluster of mbn genes with an abundance accounting for approximately 5% of Methylocystis population was identified, suggesting a comparative ecological importance of methanobactin in Cu-deficient methanotrophy over soluble methane monooxygenases. These findings highlight the importance of Methylocystis spp. in mitigating emissions from CH4 hotspots, e.g., landfills and rice paddies, and suggest the feasibility of directed enrichment/isolation of Methylocystis spp. for utilization in, for example, methanobactin and polyhydroxybutyrate production. SynopsisThis study reports enrichment of a complex soil microbiota with 0.5% methane resulting in dominance of a specific group of methane-consuming bacteria Methylocystis, highlighting their ecological significance as CH4 sink.

microbiology↗

bioRxiv2021

Intrinsic circadian timekeeping properties of the thalamic lateral geniculate nucleus

Circadian rhythmicity in mammals is sustained by the central brain clock - the suprachiasmatic nucleus of the hypothalamus (SCN), entrained to the ambient light-dark conditions through a dense retinal input. However, recent discoveries of autonomous clock gene expression cast doubt on the supremacy of the SCN and suggest circadian timekeeping mechanisms devolve to local brain clocks. Here we use a combination of molecular, electrophysiological and optogenetic tools to evaluate intrinsic clock properties of the main retinorecipient thalamic centre - the lateral geniculate nucleus (LGN). We identify the dorsolateral geniculate nucleus (DLG) as a slave oscillator, which exhibits core clock gene expression exclusively in vivo. Additionally, we provide compelling evidence for intrinsic clock gene expression accompanied by circadian variation in neuronal activity in the intergeniculate leaflet (IGL) and ventrolateral geniculate nucleus (VLG). Finally, our optogenetic experiments propose the VLG as a light-entrainable oscillator, whose phase may be advanced by retinal input at the beginning of the projected night. Altogether, this study for the first time demonstrates autonomous timekeeping mechanisms shaping circadian physiology of the LGN.

neuroscience↗

bioRxiv2021

Daily orexinergic modulation of the rat superficial layers of the superior colliculus - implications for intrinsic clock activities in the visual system

The orexinergic system delivers excitation for multiple brain centres to facilitate behavioural arousal, with its malfunction resulting in narcolepsy, somnolence, and notably, visual hallucinations. Since the circadian clock underlies the daily arousal, a timed coordination is expected between the orexin system and its target subcortical visual system, including the superior colliculus (SC). Here, we use a combination of electrophysiological, immunohistochemical, and molecular approaches across 24 h, together with the neuronal tract tracing methods in rodents to elucidate the daily coordination between the orexin system and the superficial layers of the SC. We find the daily orexinergic innervation onto the SC, coinciding with the daily silencing of spontaneous firing in this visual brain area. We identify autonomous daily and circadian expression of clock genes in the SC, which may underlie these day-night changes. Additionally, we establish the lateral hypothalamic origin of orexin innervation to the SC and that the SC neurons robustly respond to orexin A via OX2 receptor in both excitatory and GABAA receptor-dependent inhibitory manners. Together, our evidence supports that the clock coordination between the orexinergic input and its response in the SC provides arousal-related excitation needed to detect sparse visual information during the behaviourally active phase.

neuroscience↗

bioRxiv2019

Weak Coupling Between Intracellular Feedback Loops Explains Dissociation of Clock Gene Dynamics

Circadian rhythms are generated by interlocked transcriptional-translational negative feedback loops (TTFLs), the molecular process implemented within a cell. The contributions, weighting and balancing between the multiple feedback loops remain debated. Dissociated, free-running dynamics in the expression of distinct clock genes has been described in recent experimental studies that applied various perturbations such as slice preparations, light pulses, jet-lag, and culture medium exchange. In this paper, we provide evidence that this \"presumably transient\" dissociation of circadian gene expression oscillations may occur at the single-cell level. Conceptual and detailed mechanistic mathematical modeling suggests that such dissociation is due to a weak interaction between multiple feedback loops present within a single cell. The dissociable loops provide insights into underlying mechanisms and general design principles of the molecular circadian clock.

systems biology↗

bioRxiv2018

Ethane-dependent synthesis of polyhydroxyalkanoates by the obligate methanotroph Methylocystis parvus OBBP

Under conditions of nutrient-limited growth, Type II obligate methanotrophs oxidize C1 compounds, such as methane or methanol and accumulate intracellular granules of poly(3-hydroxybutyrate) (P3HB). Here, we report that, under same nutrient-limited conditions, the Type II obligate methanotroph Methylocystis parvus OBBP can use ethane as its sole carbon and energy source for synthesis P3HB granules, accumulating up to 35 {+/-} 4 wt% P3HB. 13C-NMR spectra of the P3HB confirmed incorporation of 13C from [13C2]ethane. Moreover, when valerate was added as a co-substrate with ethane, oxidation of the ethane supported synthesis of the copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV).\n\nIMPORTANCEThe presence of ethane in natural gas is often considered undesirable for methanotroph-based biotechnology due to the C1 specialization of obligate methanotrophs and concerns about inhibitory byproducts arising from methane monooxygenase-mediated cometabolism of ethane. This work establishes that co-oxidation of ethane and further metabolism in the absence of methane can support synthesis of the valuable polyhydroxyalkanoate bioplastics P3HB and PHBV.

microbiology↗