Neuronal diversity of neuropeptide signaling, including galanin, in the mouse locus coeruleus
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ABSTRACT:
PROVIDER: PRJNA990681 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25114146.fastq.gz | Fastqsanger.gz | |||
| SRR25114147.fastq.gz | Fastqsanger.gz | |||
| SRR25114148.fastq.gz | Fastqsanger.gz | |||
| SRR25114149.fastq.gz | Fastqsanger.gz |
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Project description:Purpose: The locus coeruleus (LC) is a small nucleus in the pons, with norepinephrine (NE) as its major transmitter. It plays key roles in wakefulness and is associated with disorders like depression. The study aims to analyze single-cell RNA-seq data to subdivide neurons in the LC and chart their neuropeptide, co-transmitter, and receptor profiles. It also seeks to build a precise map of galanin and its receptors in the mouse LC, and understand the role of neuropeptide expression and signaling. Results: The study identified 24 clusters in total, with 3 NE, 17 glutamate, and 5 GABA subtypes. NE neurons expressed at least 19 neuropeptide transcripts, mainly galanin (Gal) but not Npy, and >30 neuropeptide receptors. Among galanin receptors, Galr1 was expressed in ~19% of NE neurons, and highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca2+-imaging using GCaMP6s revealed that a GalR1 agonist inhibits no more than ~35% of NE neurons, with the effect being direct and not relying on feed-forward GABA inhibition. Conclusions: The results define a role for the galanin system in NE functions and provide a conceptual framework for the action of many other peptides and their receptors. The study found that most NE neurons express mRNA transcripts for galanin, at least 19 neuropeptides (but not Npy), and >30 neuropeptide receptors, including Galr1 at low levels. Selective activation of GalR1 inhibited the spontaneous activity of a subset of NE neurons possibly through the activation of Kv currents. These findings offer new insights into the role of neuropeptide expression and signaling in mouse LC.
2023-07-03 | GSE236349 | GEO
Project description:The locus coeruleus (LC) is a small nucleus in the pons from which ascending and descending projections innervate major parts of the central nervous system. Its major transmitter is norepinephrine (NE). This system is evolutionarily conserved, including in humans, and its functions are associated with wakefulness and related to disorders, such as depression. Here, we performed single-cell ribonucleic acid-sequencing (RNA-seq) to subdivide neurons in the LC (24 clusters in total) into 3 NE, 17 glutamate, and 5 γ-aminobutyric acid (GABA) subtypes, and to chart their neuropeptide, cotransmitter, and receptor profiles. We found that NE neurons expressed at least 19 neuropeptide transcripts, notably galanin (Gal) but not Npy, and >30 neuropeptide receptors. Among the galanin receptors, Galr1 was expressed in ~19% of NE neurons, as was also confirmed by in situ hybridization. Unexpectedly, Galr1 was highly expressed in GABA neurons surrounding the NE ensemble. Patch-clamp electrophysiology and cell-type-specific Ca2+-imaging using GCaMP6s revealed that a GalR1 agonist inhibits up to ~35% of NE neurons. This effect is direct and does not rely on feed-forward GABA inhibition. Our results define a role for the galanin system in NE functions, and a conceptual framework for the action of many other peptides and their receptors.
| S-EPMC10401028 | biostudies-literature
Project description:Decades of research confirm that noradrenergic locus coeruleus (LC) neurons are essential for arousal, attention, motivation, and stress responses. While most studies on LC transmission focused unsurprisingly on norepinephrine (NE), adrenergic signaling cannot account for all the consequences of LC activation. Galanin coexists with NE in the vast majority of LC neurons, yet the precise function of this neuropeptide has proved to be surprisingly elusive given our solid understanding of the LC system. To elucidate the contribution of galanin to LC physiology, here we briefly summarize the nature of stimuli that drive LC activity from a neuroanatomical perspective. We go on to describe the LC pathways in which galanin most likely exerts its effects on behavior, with a focus on addiction, depression, epilepsy, stress, and Alzheimer?s disease. We propose a model in which LC-derived galanin has two distinct functions: as a neuromodulator, primarily acting via the galanin 1 receptor (GAL1), and as a trophic factor, primarily acting via galanin receptor 2 (GAL2). Finally, we discuss how the recent advances in neuropeptide detection, optogenetics and chemical genetics, and galanin receptor pharmacology can be harnessed to identify the roles of LC-derived galanin definitively. This article is part of a Special Issue entitled SI: Noradrenergic System.
| S-EPMC4874918 | biostudies-other
Project description:Post-mortem investigations indicate that the locus coeruleus (LC) is the initial site of hyperphosphorylated pretangle tau, a precursor to neurofibrillary tangles (NFTs) found in Alzheimer's disease (AD). The presence of pretangle tau and NFTs in the LC correlates with AD progression. LC neuron integrity and quantity are linked to cognitive states, with degeneration associated with AD. However, the mechanisms of pretangle tau-induced LC degeneration are unclear. This study examined the transcriptomic and mitochondrial profiles of LC noradrenergic neurons after transduction with pseudophosphorylated human tau. Tau hyperphosphorylation increased the somatic expression of the L-type calcium channel (LTCC), impaired mitochondria health, and led to deficits in spatial and olfactory learning. Sex-dependent alterations in gene expression were observed in rats transduced with pretangle tau. Chronic LTCC blockade prevented behavioral deficits and altered mitochondrial mRNA expression, suggesting a potential link between LTCC hyperactivity and mitochondrial dysfunction. Our research provides insights into the consequences of tau pathology in the originating structure of AD.
2024-11-16 | GSE272794 | GEO
Project description:We analyzed the transcriptomic profile of post-mortem explants from dorsal nucleus of vagus nerve, locus coeruleus and substantia nigra obtained from controls and Braak 4 (BK4) and 5 (BK5) stages of Parkinson’s disease (PD) patients in order to investigate how gene-gene interaction patterns vary along different anatomical regions in patients and controls. The comparative transcriptional networks analyses indicate that the main hubs in PD networks are related to ubquitin/proteasome, oxidative stress, neuroprotection, neurogenesis and PD associated proteins. Transcriptomic profiles of controls and Parkinson’s disease patients were compared using SAM test for LC or Wilcoxon Mann-Whitney test for SN and VA (p<0.005 and p<0.01, respectively) in order to identify differentially expressed transcripts.
2015-01-11 | E-GEOD-43490 | biostudies-arrayexpress
Project description:The ciliate Stentor coeruleus microbiome
| PRJEB30974 | ENA
Project description:As the primary source of norepinephrine (NE) in the brain, the locus coeruleus (LC) regulates both arousal and stress responses, but how neuromodulatory inputs contribute to LC modulation remains incompletely understood. In this study, we isolated a network of transcriptionally diverse inhibitory pericoerulear (peri-LC) GABAergic neurons that integrate distant stimuli and modulate modes of LC firing. To define the peri-LC anatomy, we used viral tracing, single-nuclei and high-resolution spatial RNA transcriptomics to molecularly characterize both LC and peri-LC cell types. We complemented this approach with techniques in electrophysiology, photometry, optogenetics, and chemogenetics to probe the function of peri-LC neurons in behaving mice. These findings indicate that LC and peri-LC neurons comprise transcriptionally heterogenous neuronal groups which integrate diverse inputs to influence behavioral arousal states and avoidance. We used snRNAseq to characterize the peri-LC and LC brain regions. Our dataset contains 30,838 cells, of which 12,278 are neurons.
2025-01-31 | GSE201998 | GEO
Project description:Locus coeruleus vulnerability to tau hyperphosphorylation in a rat model
| PRJNA1138745 | ENA