flypapers1d ago
📰 "Metaplastic sleep regulation in Drosophila determined by microscale circadian neural dynamics"
https://www.biorxiv.org/content/10.64898/2026.03.21.713346v1?rss=1
#Drosophila #Circadian
#Sleep
Metaplastic sleep regulation in Drosophila determined by microscale circadian neural dynamics

The biophysical mechanisms by which circadian clock neurons integrate temporal coding signals to regulate sleep remain elusive. Here, using Drosophila , we identify Rabphilin (Rph) in DN1p clock neurons as a key stabilizer of the metaplasticity setpoint governing circadian regulation of sleep. Rph protein levels are elevated at night relative to daytime and modulate stochastic process of DN1p membrane potential dynamics linked to variability in synaptic activity at connections between DN1p neurons and their downstream postsynaptic partners. We find that Rph acts as a bidirectional regulator of synaptic plasticity thresholds. Under dim nocturnal light stimulation, Rph knockdown permits synaptic potentiation, whereas synthesized Rph introduction induces synaptic depression. In contrast, under optogenetic manipulation mimicking daytime spiking in DN1p neurons, these effects are reversed. We further show that spike timing dependent plasticity emerges when postsynaptic spiking is engaged, with nocturnal dim light conditions determining the direction of plasticity. Together, these findings establish a mechanistic link between microscale circadian neural dynamics and hierarchical metaplastic regulation, demonstrating how circadian regulation of sleep dynamically balances stability and adaptive flexibility through circadian setpoints and environmental nocturnal light interactions. ### Competing Interest Statement The authors have declared no competing interest. National Institute of Neurological Disorders and Stroke, R00NS101065 National Institute of General Medical Sciences, https://ror.org/04q48ey07, R35GM142490 Whitehall Foundation, https://ror.org/00her7k05 BrightFocus Foundation, A2021043S Japan Science and Technology Agency, https://ror.org/00097mb19, JPMJPR2386 Research Corporation for Science Advancement, SA-MBC-2024-080c

bioRxiv
flypapers1d ago
📰 "Drosophila core circadian clock neurons peptidergically regulate activity of insulin-producing cells"
https://www.biorxiv.org/content/10.64898/2026.03.23.713581v1?rss=1
#Drosophila #Circadian
Drosophila core circadian clock neurons peptidergically regulate activity of insulin-producing cells

Central pacemaker neurons use a combination of external stimuli and neuropeptide signaling to synchronize molecular oscillations leading to circadian behaviors. The clock network structure and signaling between these pacemaker neuron groups have been well described, but how these pacemakers communicate with specific brain output regions remains poorly understood. Here, we identified how “core” clock neurons in Drosophila, the ventrolateral neurons (LNvs), signal to the proto-hypothalamic region, the pars intercerebralis (PI). Previously thought to communicate with the PI only indirectly, we provide evidence to show that LNvs functionally modulate insulin-producing cells (IPCs) of the PI in a time-of-day-dependent manner. This functional connectivity relies on neuropeptidergic signaling of two classical clock neuropeptides: pigment dispersing factor (PDF) and short Neuropeptide F (sNPF). Connectomic analysis does not identify any direct synaptic inputs from clock neurons to IPCs. Small ventrolateral clock neurons, which secrete both PDF and sNPF are 15-20 μm away from IPCs, suggesting that volume transmission across these distances may be possible in the fly dorsal protocerebrum. Peptide application with functional imaging of IPCs provides insight into how these two neuropeptides may act synergistically via their receptors to signal to IPCs. Our findings indicate that LNvs can signal directly to IPCs by volume transmission and also form indirect multisynaptic circuits with IPCs, which may model more broadly how circadian clock peptides communicate with other clock output regions. ### Competing Interest Statement The authors have declared no competing interest.

bioRxiv
flypapers2d ago
📰 "Brain Transcriptomics Across Diverse Sleep-Wake Manipulations Reveals Multiple Homeostatic Pathways in Drosophila"
https://doi.org/doi:10.64898/2026.02.28.708752
https://pubmed.ncbi.nlm.nih.gov/41867706/
#Circadian
#Drosophila #Sleep
Brain Transcriptomics Across Diverse Sleep-Wake Manipulations Reveals Multiple Homeostatic Pathways in Drosophila

Sleep is governed by two processes: a circadian process that times sleep and wake and a homeostatic process that drives sleep as a function of prior wake history. Discovered in the fruit fly Drosophila , the period ( per ) gene is a “universal” cornerstone of the circadian clock, robustly oscillating at the transcript level, in all organs and tissues and in essentially all animals. We hypothesized that there may be a comparable factor (we term “slee-per”) for sleep homeostasis. To identify sleeper genes, we performed a wide-ranging transcriptomic analysis to identify genes whose expression tracks sleep-wake history in the Drosophila brain. We analyzed a variety of methods to manipulate sleep-wake and subsequent rebound including mechanical, thermogenetic, optogenetic, pharmacological and baseline sleep across 7 datasets. Using a log2 fold change threshold of 1, we did not identify any gene that was sleep-wake dependent across all datasets, raising the possibility that genes identified with a single method of sleep manipulation are related to the nature of the manipulation and not necessarily to sleep. Nonetheless, we did identify genes whose expression changed with sleep-wake in a consistent direction across at least 2 datasets. These analyses highlight previous processes implicated in sleep homeostasis such as mitochondrial oxidative phosphorylation as well as provide potentially novel pathways such as ribosome biogenesis. In addition, we also examined genes whose expression correlates with prior sleep-wake history and/or predicted subsequent sleep rebound across these datasets. Among significantly correlated genes we observed some that were correlated with recent (<3h) sleep history while others were correlated with much longer (>6h) time frames suggesting temporally distinct pathways for integrating waking experience. This analysis also highlights specific GO pathways for sleep/wake/rebound. Applying a novel GPT based paper search algorithm, we call fl.ai , we identified several sleep-wake regulated genes with demonstrated function in sleep regulation consistent with an in vivo homeostatic function. These include those involved in immunity, neuropeptide signaling, glucose transport, and neuronal excitability. Collectively, these studies suggest that sleep homeostasis is a much more molecularly distributed process than the core circadian clock. ### Competing Interest Statement The authors have declared no competing interest. NIH, R35NS132223, F32NS110183 Eagles Autism Foundation

bioRxiv
flypapersMar 14
📰 "Assessment of adult structural plasticity in Drosophila neurons"
https://www.biorxiv.org/content/10.64898/2026.03.11.711108v1?rss=1
#Circadian
#Drosophila #Adult
Assessment of adult structural plasticity in Drosophila neurons

Unraveling how adult neurons reshape their architecture is key to understanding post-developmental plasticity. Drosophila clock neurons, which remodel their terminals on a daily basis, offer a unique model to examine the mechanisms underlying structural plasticity. In this study, we examine the impact of the experimental design on the remodeling process. We established a simple fixation protocol that preserves tissue integrity and prevents its deformation while enabling the fixation of a larger number of individuals within the appropriate time window. We show that intrinsic (i.e., targeting fluorescent reporters to the membrane) or extrinsic (i.e., temperature) variables may influence this dynamic process. Examining ex vivo preparations, we found that the s-LNv terminals display numerous thin filopodia extending from their synaptic boutons. However, these fine membrane protrusions are lost upon fixation, as they could only be accurately visualized ex vivo. Finally, we present MorphoScope, a Python-based interface that eliminates observer bias in complexity measurements. Altogether, we present a powerful and robust model to investigate the principles of adult neuronal plasticity, with implications extending beyond circadian biology. ### Competing Interest Statement The authors have declared no competing interest. NIH, R01NS108934 Agencia Nacional de Promoción Científica y Tecnológica, PICT2018-0995

bioRxiv
Andrew MillarMar 13

Our colleagues in the #Circadian Mental Health Network comment on a research study in Trondheim 🇳🇴, by @lindageddes today in @TheGuardian:

⏬ lowering the blue light in an inpatient psychiatric ward improved the quality of treatment.

https://www.theguardian.com/science/2026/mar/13/how-the-colour-of-light-could-be-used-to-treat-mental-illness-norway

#mentalhealth #research #architecture #lighting

Out of the blue? How the colour of light could be used to treat mental illness

A psychiatric unit in Norway has been testing its built-in lighting on conditions such as psychosis and depression

The Guardian
The Perpetually Curious!Mar 13

🌱 Flowers open, forests shift, and ancient trees move through their days with a quiet sense of rhythm. What if plants keep time more subtly than our clocks?

✍️ Explore the quiet clocks of plant life: https://TPC8.short.gy/3qxzQGl1

A different kind of timekeeping waits beneath each leaf.

#Plants #Science #Circadian #Biology #Phenology #Nature #Botany #TPC8

🌿 How Plants Tell Time: The Quiet Clocks That Shape the Living World

Plants keep time with circadian clocks and seasonal cues. Explore how light, genes, and ecology shape plant rhythms.

flypapersMar 12
📰 "A day sleep promoting role of phototransduction in Drosophila melanogaster"
https://doi.org/doi:10.1016/j.nbscr.2026.100146
https://pubmed.ncbi.nlm.nih.gov/41815955/
#DrosophilaMelanogaster
#Circadian
#Drosophila #Behaviour #Sensory
#Sleep
flypapersMar 11
📰 "Anticipatory Capture of Circulating Peptidergic Vesicles in a Clock Neuron"
https://doi.org/doi:10.1091/mbc.E25-11-0558
https://pubmed.ncbi.nlm.nih.gov/41811780/
#Drosophila #Circadian
#Sleep
Robert Lufkin MDMar 8

As a medical school professor, I tell my students: "Sleep" isn't a luxury.

It's metabolic medicine.

A new NHANES analysis (n=23,475) found an inverted U-shaped curve between weekday sleep and insulin resistance (via eGDR).

The sweet spot: ~7.32 hours/night.
• Below 7.32h, more sleep improved insulin sensitivity (β=0.273 per hour)
• Above 7.32h, more sleep was linked to worse eGDR (β=−0.222 per...
#sleep #circadian #insulinresistance #metabolichealth #diabetes
https://doi.org/10.1136/bmjdrc-2025-005692

flypapersMar 8
📰 "F-53B triggers sleep disorders via very long-chain ceramide accumulation in Drosophila neurons"
https://doi.org/doi:10.1016/j.ecoenv.2026.119980
https://pubmed.ncbi.nlm.nih.gov/41793920/
#DrosophilaMelanogaster
#Circadian
#Drosophila #Sleep