Athira Theyyassanchery Mani, Vivian Backs, Christian Werner, Charlotte Helfrich-Förster, Thomas Raabe
{"title":"<i>Drosophila</i> RSK: A Pivotal Regulator of Circadian Plasticity at the Neuronal and Behavioral Level.","authors":"Athira Theyyassanchery Mani, Vivian Backs, Christian Werner, Charlotte Helfrich-Förster, Thomas Raabe","doi":"10.1177/07487304261434715","DOIUrl":"https://doi.org/10.1177/07487304261434715","url":null,"abstract":"<p><p>Circadian neuronal plasticity describes daily recurring changes at the level of neuronal morphology, connectivity and synaptic processes. Disturbance of these plastic changes could result in inflexibility of an organism to adapt behavior to changing environmental cues. The mitogen activated protein kinases (MAPK)/ERK signaling pathway is involved both in circadian processes and neuronal plasticity. Ribosomal S6 kinases (RSK) act as downstream mediators of ERK signaling with apparently pleiotropic-but sometimes poorly understood- functions in the nervous system. This is illustrated by some major gaps in our understanding of the pathophysiological processes caused by RSK2 mutations in humans that lead to intellectual disabilities. Previous studies described the role of <i>Drosophila</i> RSK as one regulator of the molecular circadian oscillator. Here we could show that RSK kinase activity is required to control another aspect of circadian rhythmicity, the daily remodeling of the dorsal branching pattern of the small ventral lateral neurons (s-LN<sub>v</sub>) as the central pacemaker cells. Loss of RSK function resulted in more fasciculated and less branched s-LN<sub>v</sub>'s in the early morning, which could affect synaptic in- or output connectivity. Increased fasciculation correlated with a reduced number of Bruchpilot sites as a marker for presynapses. Analysis of the expression of the Pigment Dispersing Factor PDF in s-LN<sub>v</sub>'s, the most important signaling factor between clock neurons, revealed no evidence of changes in <i>RSK</i> mutants. Consistent with unaffected PDF signaling as a major output from the s-LN<sub>v</sub>'s, <i>RSK</i> mutant flies are rhythmic. Their free-running rhythms show even a significantly higher power than those of the wild-type controls. This robustness is at the expense of flexibility to adapt their activity to variations in light conditions. Together with the known role of RSK in olfactory learning and memory processes our results suggest that RSK is required to maintain experience dependent plasticity.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261434715"},"PeriodicalIF":2.1,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147673602","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Itzel M Vazquez, Melissa Palomino, Lourdes M DelRosso
{"title":"Seasonal Variation in Sleep, Respiratory, and Cardiovascular Parameters Assessed by a Wearable Device.","authors":"Itzel M Vazquez, Melissa Palomino, Lourdes M DelRosso","doi":"10.1177/07487304261433622","DOIUrl":"https://doi.org/10.1177/07487304261433622","url":null,"abstract":"<p><p>Seasonal variation in sleep patterns is well recognized in PSG studies and actigraphy, yet few studies have comprehensively examined its impact on both sleep architecture and respiratory physiology using wearable technology. Circadian and environmental cues such as light exposure, temperature, and humidity may modulate sleep quality, apnea severity, and oxygenation, but large-scale, real-world data remain limited. We conducted a retrospective analysis of 2,386 home sleep studies, one study per individual, recorded between 2022 and 2025 using the SleepImage wearable system in Fresno, California. Each study was categorized by season of recording (winter, spring, summer, fall) based on start date. Key outcomes included total sleep duration, sleep latency, wake after sleep onset (WASO), mean and minimum SpO₂, apnea-hypopnea indices (sAHI3%, sAHI4%), respiratory disturbance indices (sRDI3%, sRDI4%), oxygen desaturation indices (ODI3%, ODI4%), and heart rate metrics. Analyses were adjusted for age using analysis of covariance (ANCOVA) and multiple linear regression to evaluate both main and interaction effects (<i>Season × Age</i>). Significant seasonal differences were observed in multiple parameters after adjusting for age. Sleep latency was longest in summer (836.97 ± 1007.76 sec) and shortest in fall (582.51 ± 661.49 sec, <i>p</i> < 0.001). Apnea hypopnea indices were highest in winter and lowest in fall (<i>p</i> = 0.027), while mean SpO₂ and maximum SpO₂ were modestly reduced in colder months (<i>p</i> < 0.001). Mean heart rate was higher in winter (68.3 ± 10.9 bpm) compared with summer (65.7 ± 9.3 bpm, <i>p</i> < 0.001). Interaction models revealed that age modified seasonal effects on sleep efficiency and latency, with older adults showing greater winter-related sleep latency increases but smaller seasonal fluctuations in apnea indices. Sleep and respiratory parameters exhibit distinct seasonal modulation, with winter months associated with higher apnea burden and reduced oxygenation, and summer associated with prolonged sleep latency and greater fragmentation.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261433622"},"PeriodicalIF":2.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Daily Rhythms in Clock Gene mRNA Expression in Serotonergic Brain Regions of Adult Male Rats.","authors":"Helen K Strnad, Robert L Spencer","doi":"10.1177/07487304261427042","DOIUrl":"https://doi.org/10.1177/07487304261427042","url":null,"abstract":"<p><p>Dysregulation of the serotonergic system is consistently noted in cases of psychiatric pathology. Circadian rhythm dysregulation is also a common comorbidity in psychiatric populations, and the circadian and serotonergic systems have a long history of coregulation. Despite this, it is not yet known whether serotonergic neurons house circadian molecular clocks, the transcription and translation feedback loops that drive circadian rhythms at the cellular level. To investigate this, brain tissue was extracted from adult male rats every 4 h throughout the light-dark cycle. Radiolabeled in situ hybridization was used to quantify clock gene expression in the dorsal and median raphe, the two nuclei responsible for providing the majority of serotonin to the brain. We discovered oscillatory rhythms in the expression of clock genes <i>Bmal1, Per1</i>, and <i>Per2</i> with a period of approximately 24 h, and confirmed via fluorescent in situ hybridization that serotonergic (positive for <i>Tph2</i>, the rate-limiting enzyme in serotonin synthesis) neurons do express clock genes. The roughly antiphasic relationship between <i>Bmal1</i> and the <i>Per</i> genes supports the existence of a circadian molecular clock in these cells. We next measured clock gene expression in neighboring brainstem regions that were not serotonergic, and found that although they all had similar daily clock gene expression profiles, the dorsal and median raphe had higher amplitude <i>Bmal1</i> expression, and trending higher amplitude <i>Per1</i> expression. This study adds to the growing list of extra-SCN (suprachiasmatic nucleus) molecular clocks reported in the brain. The prevalence of this circadian machinery, especially in regions of the brain so relevant to psychiatric health, underscores the importance of circadian rhythms to well-being. A greater understanding of the unique nature of circadian rhythms in discrete brain regions is a fruitful frontier for improving psychiatric treatment outcomes and overall health.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261427042"},"PeriodicalIF":2.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645126","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
K L Nikhil, Keenan Bates, Elizabeth Sapiro, Jacob L Amme, Ron McCarthy, Sarah L Speck, Varun Vasireddy, Ethan Roberts, Carmel A Martin-Fairey, Miguel-E Domínguez-Romero, Sandra P Cárdenas-García, Sarah K England, Erik D Herzog
{"title":"Fetoplacental Circadian Rhythms Develop and Then Synchronize to the Mother In Utero.","authors":"K L Nikhil, Keenan Bates, Elizabeth Sapiro, Jacob L Amme, Ron McCarthy, Sarah L Speck, Varun Vasireddy, Ethan Roberts, Carmel A Martin-Fairey, Miguel-E Domínguez-Romero, Sandra P Cárdenas-García, Sarah K England, Erik D Herzog","doi":"10.1177/07487304261435435","DOIUrl":"10.1177/07487304261435435","url":null,"abstract":"<p><p>Circadian rhythms in gene expression and hormones are ubiquitous across species and differentiated cell types, yet their developmental origins remain poorly understood. This study aimed to determine if daily rhythms can be detected in utero and if they synchronize to the mother. We developed methods to longitudinally monitor PERIOD2 (PER2), a core circadian clock protein, from embryonic day (E)8.5 to E17.5 by restricting PER2::LUCIFERASE expression to the mouse fetoplacental unit (fetus and fetal-derived tissues). In utero fetoplacental bioluminescence imaging showed that PER2 levels increased during pregnancy, with variable daily peak times that stabilized to early night by E15.5. Interestingly, pregnancies that did not exhibit daily in utero PER2 variation were more likely to fail. Because maternal glucocorticoids have been implicated in fetal development and synchronizing other circadian tissues, we tested whether glucocorticoid injections could shift fetoplacental PER2 rhythms in utero. Daily subcutaneous corticosterone injections over 5 days of late pregnancy phase-dependently shifted the fetoplacental PER2 rhythms in utero. Blocking glucocorticoid signaling in vitro reduced synchrony between maternal and fetal placenta. We conclude that in utero daily rhythms gradually develop and synchronize with the mother prior to birth, potentially through glucocorticoid signaling.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261435435"},"PeriodicalIF":2.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13078692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evolutionary Consequences of Selection on Circadian Accuracy.","authors":"Chitrang Dani","doi":"10.1177/07487304261438179","DOIUrl":"https://doi.org/10.1177/07487304261438179","url":null,"abstract":"","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261438179"},"PeriodicalIF":2.1,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Mariam Huertas-Radi, Adam A Bradlaugh, Richard A Baines
{"title":"Circadian Rhythms Time Seizure Severity in <i>Drosophila</i>.","authors":"Mariam Huertas-Radi, Adam A Bradlaugh, Richard A Baines","doi":"10.1177/07487304261428337","DOIUrl":"https://doi.org/10.1177/07487304261428337","url":null,"abstract":"<p><p>It is established that epilepsy patients can exhibit 24-h rhythms in seizure severity and occurrence. While the pathways underlying seizure rhythmicity remain poorly understood, it seems likely that a contribution from the biological clock is involved. A better understanding of any such contribution may translate to better treatments. Here, the influence of the 24-h circadian rhythm on seizure activity in <i>Drosophila melanogaster</i> is investigated. Seizure-susceptible bang-sensitive mutants (<i>julius seizure</i> and <i>paralytic<sup>bangsenseless1</sup></i>) were subjected to mechanically induced seizure at 6 different zeitgeber points. A clear sex-dependent phenotype was observed, with seizure severity showing a greater time-of-day effect in females than males. The temporal pattern of seizure recovery time was bimodal, exhibiting both a morning and an evening peak. Rearing flies in constant light (LL), which renders the molecular clock dysfunctional, abolished the seizure rhythm. Conversely, female seizure mutants reared in constant darkness (DD), allowing free running of the circadian clock, continued to exhibit a bimodal rhythm of seizure severity. Moreover, seizure mutant females lacking a functional clock (<i>period<sup>0</sup></i>) did not show rhythmicity of seizure severity. These findings support a role for the biological clock in seizure activity, at least in female <i>Drosophila</i>. Finally, seizure mutant females showed normal PERIOD clock protein intensity oscillations in clock neurons, supporting the hypothesis that seizure rhythmicity requires a functional circadian clock. Thus, this study validates <i>Drosophila</i> as a potential model for the identifying the mechanisms modulating seizure rhythmicity, with the potential to aid future treatment of epilepsy.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261428337"},"PeriodicalIF":2.1,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147645104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Actigraphy-Based Movement Profiles and Their Association With Circadian Rhythms Integrity in Real-World Settings.","authors":"Mariana Marchesano, Ana Silva, Bettina Tassino","doi":"10.1177/07487304261428332","DOIUrl":"https://doi.org/10.1177/07487304261428332","url":null,"abstract":"<p><p>Both active movement profiles and robust circadian rhythms are linked to improved health outcomes, yet the underlying mechanisms remain partially understood. We investigated this relationship in young adults (<i>n</i> = 169, aged 18-30 years) under real-world conditions using actigraphy data. We performed k-means clustering on 12 accelerometer-based features capturing magnitude, duration, frequency, and intensity distribution to derive movement behavior profiles. As a proxy of circadian rhythms integrity, we computed the Circadian Function Index (CFI), which combines intradaily variability, interdaily stability, and relative amplitude. We also assessed circadian phase and sleep quality parameters. In addition, we quantified light exposure and physical activity over 3-h daily intervals. The unsupervised algorithm identified 2 non-overlapping profiles among participants, the More Active (MA) and the Less Active (LA) profiles. MA exhibited a higher CFI (0.81 ± 0.06 vs 0.69 ± 0.06, <i>p</i> < 0.001), which was also positively associated with early-evening physical activity, but not with light exposure. MA also showed an earlier activity-based phase indicator, the midpoint of the 5 least-active hours (L5c, 04:30 ± 01:03 vs 04:59 ± 01:15, <i>p</i> adj. = 0.04), which was inversely associated with early-morning physical activity and late-morning light exposure. We found no differences in sleep quality between MA and LA. Our results underscore the association between movement behavior and overall circadian rhythms integrity. Importantly, these findings reinforce actigraphy as a multidimensional tool for both health research and clinical applications.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261428332"},"PeriodicalIF":2.1,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147628059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lindsay Stager, Caroline Gredvig-Ardito, Stephanie Crowley, Ronald Seifer, Mary Carskadon, Jared Saletin
{"title":"Overnight Motor Memory Consolidation in Adolescents: Effects of Change in Dim Light Melatonin Onset After Sleep Restriction.","authors":"Lindsay Stager, Caroline Gredvig-Ardito, Stephanie Crowley, Ronald Seifer, Mary Carskadon, Jared Saletin","doi":"10.1177/07487304261427822","DOIUrl":"10.1177/07487304261427822","url":null,"abstract":"<p><p>Adolescents experience chronic sleep restriction and developmental changes in circadian biology. Sleep aids adolescent learning and memory; the moderating effect of circadian rhythms is largely unknown. Here we examine adolescent sleep restriction, circadian biology, and memory consolidation. Adolescents were recruited for a larger experimental study. This study includes a subsample of individuals from the larger study who completed the motor sequence task (MST; added toward the end of data collection). Participants (<i>M</i><sub>AGE</sub> = 12.7, <i>SD</i> = 1.8; 62.5% male) completed a self-selected 9 h in bed sleep stabilization schedule for 19 nights followed by 7 nights of sleep restriction (6 h in bed; bedtime delayed and risetime advanced equally). In-lab dim light melatonin onset (DLMO) was assessed on the final nights of stabilization and restriction. The MST indexed overnight memory consolidation across the final night of sleep restriction. MST outcomes included the average number of correct sequences per trial, # of errors, and precision. We examined overnight improvement (morning-evening) in MST performance and associations between improvement, phase preference, DLMO<sub>Stabilization</sub>, DLMO<sub>Restriction</sub>, and DLMO<sub>Shift</sub> (DLMO<sub>Stabilization</sub> - DLMO<sub>Restriction</sub>), controlling for age where statistically justified. The average number of correct sequences per MST trial improved, <i>t</i>(15) = -3.44, <i>p</i> < 0.01, <i>d</i> = 0.86, for the morning (12.94 ± 6.89) test session compared to evening (10.81 ± 5.69). There were no changes in errors or precision (<i>d</i>s < 0.14, <i>p</i>s > 0.34). Greater delays in DLMO phase (<i>M</i> ± <i>SD</i>: 10.34 ± 41.69 min) were associated with greater overnight improvement in the average number of correct sequences per trial, Adj. <i>R</i><sup>2</sup> = 0.54, <i>F</i>(2, 13) = 9.79, <i>p</i> < 0.01, and errors, Adj. <i>R</i><sup>2</sup> = 0.21, <i>F</i>(1, 15) = 4.94, <i>p</i> < 0.05. Overnight improvement was not related to phase preference (Adj. <i>R</i><sup>2</sup>s < 0.17; <i>p</i>s > 0.05). These data highlight context dependent benefits of sleep for adolescent memory consolidation and indicate a potential link between circadian biology and the cognitive benefits of adolescent sleep. Understanding the influence of circadian rhythms in sleep-dependent memory may inform discussions of adolescent sleep loss and learning.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261427822"},"PeriodicalIF":2.1,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13060023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147627052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dongju Lim, Juhyeon Kim, Jee Hyun Kim, Jae Kyoung Kim
{"title":"Initial Condition Decision to Ensure Reliable Circadian Phase Estimation With Shorter-Term Wearable Data.","authors":"Dongju Lim, Juhyeon Kim, Jee Hyun Kim, Jae Kyoung Kim","doi":"10.1177/07487304261430123","DOIUrl":"https://doi.org/10.1177/07487304261430123","url":null,"abstract":"<p><p>Various studies in the medical field highlight the importance of circadian medicine, which optimizes treatment timing based on patients' circadian phases. While the circadian phase has been measured using dim light melatonin onset (DLMO), the gold standard marker, its high cost and time-intensive nature have led to the development of alternative estimation methods. Among these, the most promising method is using ordinary differential equation (ODE) models, which simulate the circadian rhythm by using a light exposure profile estimated from sleep data. These ODE models require an initial condition (IC) representing the initial state of the circadian rhythm, which is unknown in real-world settings. However, it is unclear how the uncertainty of IC affects the accuracy of circadian phase estimation. In this study, by using sleep data collected from 28 shift workers using ActiWatch (mean duration = 56 days, range = 34-75 days), we found that ≥18 days of sleep data are required for the circadian phase to become independent of the subjective IC choice. The result showed that without an accurate IC, circadian phase estimation is dependent on subjective IC choice, meaning that circadian phase estimates in the first 17 days are not reliable. Indeed, these days were reduced to 11-14 days on average when previous studies' IC estimation methods were used. To further shorten this length, we developed new IC estimation methods-period-based and work history-based sleep methods-that incorporate daily variations in sleep history. Notably, the new methods reduced the number of days required for reliable circadian phase estimation to about 5 days. Hence, our approach allows a larger portion of circadian phase estimates from given sleep data to be used as reliable information. The superiority of our methods paves the way for improved circadian phase estimation, ultimately enhancing the practicality of chronotherapy applications.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"7487304261430123"},"PeriodicalIF":2.1,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147609103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Evening Activity Termination Timing in <i>Drosophila melanogaster</i>: Effects of Pigment-Dispersing Factor-Containing Large and Small Ventrolateral Neurons.","authors":"Tatsuya Yokosako, Aika Saito, Taishi Yoshii","doi":"10.1177/07487304251388700","DOIUrl":"10.1177/07487304251388700","url":null,"abstract":"<p><p>In animals, the brain contains circadian clock neurons that regulate activity rhythms. The fruit fly <i>Drosophila melanogaster</i> exhibits a bimodal activity pattern characterized by two peaks, in the morning (M) and evening (E), known as the M and E peaks. These activity peaks are orchestrated by a network of approximately 240 clock neurons. The neuropeptide pigment-dispersing factor (PDF) is expressed in two sets of clock neurons, the large ventrolateral neurons (l-LN<sub>v</sub>) and the small ventrolateral neurons (s-LN<sub>v</sub>). Mutants of <i>Pdf</i>, as well as flies lacking PDF neurons, exhibit a characteristic E activity that is commonly simplified to a phase-advanced pattern under 12 h:12 h light-dark cycles. Previous studies have demonstrated that l-LN<sub>v</sub> neurons regulate the phase of the E peak; however, this effect is evident only under long photoperiod conditions. Therefore, the E peak phenotype observed in <i>Pdf</i> mutants remains incompletely explained. In this study, we employed genetic cell ablation and <i>Pdf</i> RNA interference using Gal4 lines specific to l-LN<sub>v</sub> neurons in a well-controlled genetic background. Under long photoperiod conditions, flies lacking l-LN<sub>v</sub>, s-LN<sub>v</sub>, or both neuronal groups exhibited an early termination of E activity prior to lights-off, resulting in a phase-advanced E peak. Similar results were obtained in <i>Pdf</i> knockdown flies. Notably, l-LN<sub>v</sub> neurons had a stronger effect on the timing of E activity termination than s-LN<sub>v</sub> neurons. These findings demonstrate that LN<sub>v</sub> neurons control the phase of E activity by modulating the timing of its offset, providing new insights into the neuronal mechanisms that shape daily activity patterns.</p>","PeriodicalId":15056,"journal":{"name":"Journal of Biological Rhythms","volume":" ","pages":"243-258"},"PeriodicalIF":2.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145762927","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}