Pde10a gates light responses in the SCN to regulate circadian photoentrainment
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE287917 | GEO | 2026/01/23
REPOSITORIES: GEO
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Project description:One hundred ninety wildtype male C57BL/6J mice age 7-10 weeks were purchased from Jackson Laboratory and entrained to a 12:12 light:dark cycle for 2 weeks. Mice were placed in light-tight boxes on a 12:12 LD cycle for 4 weeks, then released into constant darkness. Starting 30 hours after entry into DD (CT18), tissues from 5 (skeletal muscle) or 10 (liver or SCN) wildtype mice were collected every 4 hours for 48 hours, for a total of 12 timepoints. At timepoints 34 through 58 hours in DD, tissues from age-matched male C57BL/6J Clock/Clock homozygous mutant mice that had been treated with the same light entrainment protocol as the wildtype were collected. Tissues were collected from 5 Clock/Clock mutants at each timepoint except for 34 and 46 hours after the onset of DD, when tissues from 10 Clock/Clock mice were collected and run as independent replicates. Mice were sacrificed by cervical dislocation, and the optic nerves were severed in complete darkness; brain dissection was performed using illumination from an infrared viewer (FJW Industries, Palatine, IL). SCNs were dissected out, pooled at a density of 5 per tube in 100 ul RNAlater (Ambion, Austin, TX), frozen on dry ice, and stored at â80 degrees C until use. Keywords: SuperSeries This reference Series links data in the following related Series: GSE3746 Circadian skeletal muscle_wt and Clock mutants GSE3748 Circadian liver_wt and Clock mutants
2010-06-12 | E-GEOD-3751 | biostudies-arrayexpress
Project description:Glaucoma is a chronic optic neuropathy characterized by the progressive de- generation of retinal ganglion cells (RGC). These cells play a crucial role in transmitting visual and non-visual information to brain regions, including the su- prachiasmatic nucleus (SCN), responsible for synchronizing biological rhythms. To understand how glaucoma affects circadian rhythm synchronization, we in- vestigated potential changes in the molecular clock machinery in the SCN. We found that the progressive increase in intraocular pressure (IOP) negatively correlated with spontaneous locomotor activity (SLA). Transcriptome analy- sis revealed significant alterations in the SCN of glaucomatous mice, including downregulation of genes associated with circadian rhythms. In fact, we showed a loss of diurnal oscillation in the expression of vasoactive intestinal peptide (Vip), its receptor (Vipr2), and period 1 (Per1) in the SCN of glaucomatous mice. These findings were supported by the 7-h phase shift in the peak expression of arginine vasopressin (Avp) in the SCN of mice with glaucoma. Despite maintaining a 24-h period under both light/dark (LD) and constant dark (DD) conditions, glaucoma- tous mice exhibited altered SLA rhythms, characterized by decreased amplitude. Taken altogether, our findings provide evidence of how glaucoma affects the regulation of the central circadian clock and its consequence on the regulation of circadian rhythms.
2024-10-23 | GSE268323 | GEO
Project description:The mammalian master circadian pacemaker within the suprachiasmatic nucleus (SCN) maintains tight entrainment to the 24 hr light/dark cycle via a sophisticated clock-gated rhythm in the responsiveness of the oscillator to light. Intriguingly, entrainment is not merely a passive response, instead the internal oscillator responds and adjust its own timing to entrainment signals discriminating the time of day. For example, exposure to brief light pulses in the first and final hours of the subjective generate circadian phase delays and advances respectively; whereas similar photic pulses during the subjective day does not modify the phase. A central event in this light entrainment process appears to be the rapid induction of gene expression via the ERK/MAPK pathway. We used microarray-based expression profiling of the suprachiasmatic nucleus to examine the role of MAPK signaling in the light-evoked transcriptional response. We focused on three circadian timepoints that define the unique, clock-time delimited response properties of the SCN to light: the subjective day, early subjective night, and late subjective night.
2021-03-24 | GSE165799 | GEO
Project description:Mammalian circadian behaviors are orchestrated by suprachiasmatic nucleus (SCN) in the hypothalamus. Yet basic SCN cell types and their roles in circadian pacemaking are still unclear. In this study, we comprehensively characterized the basic cell types of SCN and their circadian and light-induced gene expression. In SCN, we identified seven major cell types among which neurons, astrocytes, ependymocytes and endothelial cells display cell-type specific circadian gene expression. We found that five SCN neuron subtypes, Avp+/Nms+, Vip+/Nms+, Vip+/Grp+, Cck+/C1ql3+ and Cck+/Bdnf+, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Among the rhythmic neuron subtypes, we observed a wave of circadian gene expression propagating from the subtypes in posterior SCN to the subtypes in anterior SCN. Such wave can be explained by the neuropeptide-receptor signaling network in which Avp+/Nms+ subtype is the leader of circadian oscillations. Our study provides insights into the basic neural mechanism of circadian pacemaking in mammals.
2019-06-19 | GSE132608 | GEO
Project description:Mammalian circadian behaviors are orchestrated by suprachiasmatic nucleus (SCN) in the hypothalamus. Yet basic SCN cell types and their roles in circadian pacemaking are still unclear. In this study, we comprehensively characterized the basic cell types of SCN and their circadian and light-induced gene expression. In SCN, we identified seven major cell types among which neurons, astrocytes, ependymocytes and endothelial cells display cell-type specific circadian gene expression. We found that five SCN neuron subtypes, Avp+/Nms+, Vip+/Nms+, Vip+/Grp+, Cck+/C1ql3+ and Cck+/Bdnf+, differ in their spatial distribution, circadian rhythmicity and light responsiveness. Among the rhythmic neuron subtypes, we observed a wave of circadian gene expression propagating from the subtypes in posterior SCN to the subtypes in anterior SCN. Such wave can be explained by the neuropeptide-receptor signaling network in which Avp+/Nms+ subtype is the leader of circadian oscillations. Our study provides insights into the basic neural mechanism of circadian pacemaking in mammals.
2019-06-19 | GSE117295 | GEO
Project description:Circadian rhythm governs a variety of biological processes in essentially all living organisms and microRNAs have been found to play important roles in the post-transcriptional regulation of circadian clocks. However, the microRNA expression profile in mouse central circadian clock – suprachiasmatic nucleus (SCN) is lacking. In this study, we systematically profiled microRNAs in mouse SCN and SCN subtype neurons by high sensitive small RNA sequencing and examined their potential circadian functions. We found that a large fraction of known microRNAs are SCN-specific and 20 of them are also oscillated significantly. Predicted targets of these 20 microRNAs were enriched in circadian rhythm pathway as well. Integrated analysis of microRNA and mRNA revealed 3 clock-related functional modules, demonstrating the regulation roles of miR-24, miR-30, miR-7a, miR-7b, miR125a and miR125b in SCN. Furthermore, we observed distinct microRNA profiles in SCN subtype neurons with divergent regulatory functions, which correlated with their differential spatial distribution. In addition, we also identified a proportion of light-response microRNAs in SCN, one of which was miR-7a. Further experiments showed that miR-7a directly target fos and regulated its translation in SCN. All these observations indicate important circadian regulation roles of microRNA in central circadian clock.
2021-08-18 | GSE133051 | GEO
Project description:The brain’s suprachiasmatic nucleus (SCN) is the master clock driving circadian rhythms in mammals. Vasoactive intestinal polypeptide (VIP) and its cognate receptor, VPAC2, are expressed in SCN neurons and mice with genetically targeted deletion of VPAC2 (Vipr2 -/-animals) show aberrant resetting to light, abnormal behavioral rhythms, and diminished SCN clock gene expression. Timed daily access to a running-wheel (scheduled voluntary exercise; SVE) promotes Vipr2 -/- SCN clock cell synchrony and 24h behavioral rhythms. We hypothesized that timed exercise alters the SCN transcriptome. Here, in control (Vipr2+/+) and Vipr2-/- mice under freely exercising and SVE conditions, RNAseq and qRT-PCR were used to measured gene expression of laser-dissected SCN. Compared to Vipr2+/+ mice, hundreds of genes were differentially expressed in the SCN from Vipr2-/- mice rhythmic in the freely exercising condition. Unexpectedly, SVE did not promote a Vipr2+/+-like SCN transcriptome in Vipr2-/- mice and many transcripts involved in SCN function including Avp, C1ql3, Gpr176, Prok2, Sst, Per2, and Nr1d1 remained dysregulated in the SVE condition. By contrast, circadian oscillators in the liver and lung were mostly intact in Vipr2-/- mice. This study indicates that marked molecular deficits in the SCN are sustained in behaviorally rhythmic Vipr2-/- mice, raising the possibility that a minimal functional SCN circadian clock can underpin whole animal rhythms.
2023-01-20 | GSE207992 | GEO
Project description:Although the mammalian rest-activity cycle is controlled by a "master clock" in the suprachiasmatic nuclei (SCN) of the hypothalamus, it is unclear how firing of individual SCN neurons gates individual features of daily activity. Here, we demonstrate that a specific transcriptomically identified population of mouse VIP+ SCN neurons is active at the "wrong" time of the day -nighttime- when most SCN neurons are silent. Using chemogenetic and optogenetic strategies, we show that these neurons and their cellular clocks are necessary and sufficient to gate and time nighttime sleep, but have no effect upon daytime sleep. We propose mouse nighttime sleep, analogous to the human siesta, is a "hard-wired" property gated by specific neurons of the master clock to favor subsequent alertness prior to dawn (a circadian "wake maintenance zone"). Thus, the SCN is not simply a 24h metronome: specific populations sculpt critical features of the sleep-wake cycle.
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Project description:The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here we show that cochlear rhythms are system-driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Since the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and that GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses.
2019-06-15 | GSE107086 | GEO
Project description:The cochlea possesses a robust circadian clock machinery that regulates auditory function. How the cochlear clock is influenced by the circadian system remains unknown. Here we show that cochlear rhythms are system-driven and require local Bmal1 as well as central input from the suprachiasmatic nuclei (SCN). SCN ablations disrupted the circadian expression of the core clock genes in the cochlea. Since the circadian secretion of glucocorticoids (GCs) is controlled by the SCN and that GCs are known to modulate auditory function, we assessed their influence on circadian gene expression. Removal of circulating GCs by adrenalectomy (ADX) did not have a major impact on core clock gene expression in the cochlea. Rather it abolished the transcription of clock-controlled genes involved in inflammation. ADX abolished the known differential auditory sensitivity to day and night noise trauma and prevented the induction of GABA-ergic and glutamate receptors mRNA transcripts. However, these improvements were unrelated to changes at the synaptic level suggesting other cochlear functions may be involved. Due to this circadian regulation of noise sensitivity by GCs, we evaluated the actions of the synthetic glucocorticoid dexamethasone (DEX) at different times of the day. DEX was effective in protecting from acute noise trauma only when administered during daytime, when circulating glucocorticoids are low, indicating that chronopharmacological approaches are important for obtaining optimal treatment strategies for hearing loss. GCs appear as a major regulator of the differential sensitivity to day or night noise trauma, a mechanism likely involving the circadian control of inflammatory responses.
2019-06-15 | GSE88954 | GEO