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Suprachiasmatic VIP neurons are required for normal circadian rhythmicity with a subset expressing a molecularly distinct pacemaker profile

ABSTRACT: Suprachiasmatic VIP neurons are required for normal circadian rhythmicity with a subset expressing a molecularly distinct pacemaker profile

PROVIDER: PRJNA633546 | ENA |

REPOSITORIES: ENA

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Suprachiasmatic VIP neurons are required for normal circadian rhythmicity with a subset expressing a molecularly distinct pacemaker profile

Project description:The hypothalamic suprachiasmatic (SCN) clock contains several neurochemically defined cell groups that contribute to the genesis of circadian rhythms. Using cell specific and genetically-targeted approaches we have confirmed an indispensable role for vasoactive intestinal polypeptide expressing SCN (SCNVIP) neurons in generating the mammalian locomotor activity (LMA) circadian rhythm. Optogenetic-assisted circuit mapping revealed functional, di-synaptic connectivity between SCNVIP neurons and dorsomedial hypothalamic neurons, providing a circuit substrate by which SCNVIP neurons may regulate LMA rhythms. In vivo photometry revealed that while SCNVIP neurons are acutely responsive to light, their activity is otherwise behavioral state invariant. Single-nuclei RNA-sequencing revealed SCNVIP neurons comprise two transcriptionally distinct subtypes, including putative pacemaker and non-pacemaker populations. Given that SCNVIP neurons constitute ~10% of the total SCN population, and that other cell groups were unable to sustain coherent circadian LMA rhythms following SCNVIP disruption, our findings demonstrate a disproportionately large influence of the SCNVIP cell population on pacemaker function.

2020-05-19 | GSE150770 | GEO

Suprachiasmatic VIP neurons are required for normal circadian rhythmicity and comprised of molecularly distinct subpopulations.

Project description: Not available

| S-EPMC7468160 | biostudies-literature

Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus

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

Spatiotemporal single-cell analysis of gene expression in the mouse suprachiasmatic nucleus

2019-06-19 | GSE117295 | GEO

DUSP4 regulates input to the suprachiasmatic circadian network via VIP-induced activation of the ERK1/2 pathway

Project description:Analysis of the genes and cellular signalling cascades mediating the response of SCN slices to vasoactive intestinal peptide (VIP). Primary goal was to find novel genes that may be involved in circadian phase shifting for further study. Promoter analysis of significantly regulated genes and gene ontology analysis would provide information into pathways VIP acts through in the SCN.

2019-02-07 | GSE113797 | GEO

NPAS4 regulates the transcriptional response of suprachiasmatic nucleus neurons to photic input

Project description:In mammals, the hypothalamic suprachiasmatic nucleus (SCN) is the master circadian pacemaker. It is primarily entrained by environmental photic stimuli. However, the molecular bases of the response of heterogeneous cells in the SCN to photic stimuli is not fully understood. In this study, we combined bulk RNA/ChIP/single nuclei sequencing with circadian behavioral assays to investigate cellular identities in the SCN and explore how they react to photic stimuli. We identified 3 major peptidergic cells in the SCN, Avp-expressing, Vip-expressing and Cck-expressing cells. In each peptidergic cell type, there is a light responsive cell cluster, and each of these is enriched for Neuronal PAS Domain Protein 4 (NPAS4) target genes. In addition, Npas4 null mice have a 1hr longer circadian period in constant darkness and a damped phase responsive curve to photic stimuli. Bulk RNA seq in Npas4-/- SCN revealed a reduced magnitude of light induced gene expression. Together, our data indicate that NPAS4 is part of the machinery that orchestrates the molecular response to photic stimuli in the SCN.

2021-08-23 | GSE148252 | GEO

DUSP4 regulates input to the suprachiasmatic circadian network via VIP-induced activation of the ERK1/2 pathway

Project description:DUSP4 regulates input to the suprachiasmatic circadian network via VIP-induced activation of the ERK1/2 pathway

| PRJNA454006 | ENA

RNA-seq of Mus musculus to investigate the role of RNA editing for the gene expression in the suprachiasmatic nuclei of the hypothalamus

Project description:RNA editing is essential for the formation of functional properties of ionotropic glutamate channels. Previously, we demonstrated the regulation of RNA editing upon manipulation with neural activity in vitro. The hypothalamic suprachiasmatic nuclei (SCN), which serve as a master circadian pacemaker depends on glutamatergic neurotransmission, in particular for signal transmission from the retina, and they exhibit spontaneous 24h rhythmical neural activity. We observed changes in the extent of ionotropic glutamate receptor RNA editing in the SCN during the 24h cycle. Therefore, we aimed to understand the overall role of RNA editing for the mechanism of SCN function and to evaluate the impact of RNA under editing on gene expression.

2023-06-29 | E-MTAB-11408 | biostudies-arrayexpress

Light-induced Changes in the Suprachiasmatic Nucleus Transcriptome Regulated by the ERK/MAPK Pathway

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

Arabidopsis WT and vip mutants (vip5 and vip6)

Project description:Comparison of gene expression profiles of wild-type, vip5 mutant, and vip6 mutant Arabidopsis. Keywords = VIP Keywords: repeat sample

2004-09-01 | GSE1516 | GEO

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