Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional profiling of mammalian habenula using scRNAseq

ABSTRACT: The habenula complex is appreciated as a critical regulator of motivated and pathological behavioral states via its output to midbrain nuclei. Despite this, transcriptional definition of cell populations that comprise both the medial (MHb) and lateral habenular (LHb) subregions in mammals remain undefined. To resolve this, we performed single-cell transcriptional profiling and highly multiplexed in situ hybridization experiments of the mouse habenula complex in naïve mice and those exposed to an acute aversive stimulus. Transcriptionally distinct neuronal cell types identified within the MHb and LHb, were spatially defined, and differentially engaged by aversive stimuli. Cell types identified in mice, also displayed a high degree of transcriptional similarity to those previously described in zebrafish, highlighting the well conserved nature of habenular cell types across the phylum. These data identify key molecular targets within habenula cell types, and provide a critical resource for future studies. We applied scRNAseq to unbiasedly characterize mammalian habenula transcriptome. We obtained transcriptional dataset of 11,878 cells including 5,558 neuronal cells.

ORGANISM(S): Mus musculus

PROVIDER: GSE137478 | GEO | 2020/03/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

single-cell transcriptional profiling of the murine habenular complex

Project description:The lateral habenula (LHb) is an epithalamic brain structure critical for processing and adapting to negative action outcomes. However, despite the importance of LHb to behavior and the clear anatomical and molecular diversity of LHb neurons, the neuron types of the habenula remain unknown. Here, we use high-throughput single-cell transcriptional profiling, monosynaptic retrograde tracing, and multiplexed FISH to characterize the cells of the mouse habenula. We find five subtypes of neurons in the medial habenula (MHb) that are organized into anatomical subregions. In the LHb, we describe four neuronal subtypes and show that they differentially target dopaminergic and GABAergic cells in the ventral tegmental area (VTA). These data provide a valuable resource for future study of habenular function and dysfunction and demonstrate neuronal subtype specificity in the LHb-VTA circuit.

2020-03-15 | GSE146983 | GEO

Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (mRNA)

Project description:After intarvenouse catheter surgery, nicotine self-administration using an operant self-administration chamber, was conducted for 44 days with various doses of nicotine solution. Age-matched mice were used for control. After the self-administration, the Lateral Habenual (LHb) and the Medial Habenula (MHb) of the mouse brain were collected. We used microarrays to detail the mRNA expression profile of the Lateral Habenual (LHb) and the Medial Habenula (MHb) after the nicotine self-administration.

2015-03-04 | E-GEOD-66451 | biostudies-arrayexpress

Smart-seq2 analysis of larval zebrafish habenula from the gng8-GFP transgenic line

Project description:The identification of cell types and marker genes is critical for dissecting neural development and function, but the size and complexity of the brain has hindered the comprehensive discovery of cell types. We combined single-cell RNA-seq with anatomical brain registration to create a comprehensive map of the zebrafish habenula, a conserved forebrain hub involved in pain processing and learning. Single-cell transcriptomes of ~13000 habenular cells (>4x coverage) identified 18 neuronal types and dozens of marker genes. Registration of marker genes onto a common reference atlas created a rich resource for anatomical and functional studies and enabled the mapping of active neurons onto neuronal types following aversive stimuli. Strikingly, despite brain growth and functional maturation, cell types were retained between the larval and adult habenula. This study provides a gene expression atlas to dissect habenular development and function and offers a general framework for the comprehensive characterization of other brain regions.

2018-03-23 | GSE109159 | GEO

10X genomics analysis of adult and larval habenula from the gng8-GFP transgenic line

2018-03-23 | GSE109158 | GEO

Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (microRNA)

2015-03-04 | GSE66452 | GEO

Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (mRNA)

2015-03-04 | GSE66451 | GEO

Hedgehog Interaction Protein Acts in the Habenula to Regulate Nicotine Intake

Project description:Medial habenular (mHb) cholinergic neurons that project to the interpeduncular nucleus (IPn) regulate aversive behavioral responses to nicotine that protect against tobacco addiction. Little is known about the nicotine-evoked cellular or molecular adaptations in these neurons that influence the development of the smoking habit. Using in vivo calcium imaging and single-cell RNA sequencing, we show that a dose of nicotine that stimulates mHb neural activity evokes robust transcriptional plasticity in neuronal and non-neuronal cells in the mHb, including upregulated expression of Hedgehog-interacting protein (HHIP) in putative cholinergic neurons. Allelic variation in HHIP confers risk for smoking-related diseases including chronic obstructive pulmonary disease and lung cancer, but underlying mechanisms of action are unclear. Using Translating Ribosome Affinity Purification (TRAP) sequencing and RNAscope, we confirmed that Hhip transcripts are highly enriched in mHb cholinergic neurons. HHIP mutant mice exhibit hundreds of differentially expressed transcripts in the mHb and perturbed transcriptional responses to nicotine. Moreover, acute in vivo CRISPR/Cas9-mediated genomic cleavage of mHb Hhip attenuated noxious responses to nicotine and increased intravenous nicotine self-administration behavior in mice. In vitro knockdown of Hhip reduces intracellular calcium release to nicotine and increases Gli activity. These findings suggest that HHIP acts in the mHb to regulate nicotine intake and that HHIP alleles may increase vulnerability to smoking-related diseases by modulating mHb signaling and enhancing the addictive properties of tobacco.

2022-11-06 | GSE217000 | GEO

Single-nucleus transcriptional profiling of Gad2-positive neurons from the mouse lateral habenula with distinct expression of neurotransmitter-related genes

Project description:Glutamatergic projection neurons of the lateral habenula (LHb) effect behavioral statemodulation by regulating the activity of midbrain monoaminergic neurons. Identifying circuit mechanisms that control LHb output is of interest for understanding motivated behaviors. A small population of neurons within the medial subnucleus of the mouse LHb express the GABAergic synthesizing enzyme GAD2 and are capable of inhibiting nearby LHb projection neurons. However, these neurons lack most markers of classic inhibitory interneurons, and they co-express the vesicular glutamate transporter VGLUT2. To determine the molecular phenotype of these neurons, we genetically tagged the nuclei of GAD2-positive cells and used fluorescence-activated nuclear sorting followed by single nuclear RNA sequencing (FANS-snRNAseq) to determine the full transcriptional profile of GAD2+ neurons isolated from LHb. Our data demonstrate that LHb GAD2+ neurons co-express markers of both glutamatergic and GABAergic transmission and that they are transcriptionally distinct from GABAergic interneurons or habenular glutamatergic neurons. We show sex-specific differences in gene expression in this neuronal population and find that these gene sets are enriched for genes involved in depression. Finally, we identify the Ntng2 gene encoding the cell adhesion protein Netrin-G2 as a selective marker of LHb GAD2+ neurons that may contribute to their target projections. These data show the value of using genetic enrichment of rare cell types for transcriptome studies, and they advance understanding of the molecular composition of a functionally important class of neurons in the LHb.

2022-11-08 | GSE179198 | GEO

A neural substrate for negative affect dictates female parental behaviour

Project description:Parental behaviours are essential to secure survival and wellbeing of newborns. Concomitantly, parenting also limits negative affective states in adults, which emerge when the coping with neonatal distress becomes a challenge. Whether neural circuits that process negative affect orchestrate components of parental behaviours remains, however, unknown. Here, we identify functional and transcriptional signatures of parental behaviours in neurons of the negative emotion center lateral habenula receiving bed nucleus of the stria terminalis innervation (BNSTLHb). Calcium imaging and optogenetic manipulations reveal that LHb neurons of virgin female mice increase their activity in response to pup distress vocalization and are necessary for pup calls-driven aversive behaviours. Accordingly, LHb activity rises during the retrieval of a pup to a nest, a behaviour worsened by optogenetic LHb inactivation. Intersectional cell identification and transcriptional profiling associates the BNSTLHb neuronal population to parental behaviours and outlines gene expression in female virgins that is similar to mothers but divergent from non-parental virgin male mice. Accordingly, optogenetic activation and inactivation of the BNST-LHb pathway maximizes and suppresses, respectively, the parental behaviour. Finally, tracking and manipulating single BNSTLHb cell activity demonstrates specificity of this neuronal subset for encoding negative affect and pup retrieval, but not sociability amongst conspecifics. Thus, BNSTLHb cells are operational for female parenting, demonstrating that a negative affect neural circuit processes newborn distress signals and limits them through female parenting.

2023-01-04 | GSE222064 | GEO

Relapse to cocaine-seeking is regulated by medial habenula Nr4a2

Project description:After exposure to drugs of abuse, the reward circuit can experience persistent changes that are thought to underlie relapse behavior. These changes can be epigenetic in nature, and here we identify an epigenetic regulator of memory processes, nuclear orphan receptor subfamily4 groupA member2 (NR4A2 aka NURR1), as necessary for relapse to cocaine-seeking behavior. Nr4a2 is an epigenetically regulated immediate early gene and transcription factor that is highly expressed in the medial habenula (MHb). Despite the well-studied contributions of the MHb to nicotine-associated behaviors, the MHb is not classically included in reward circuits. Therefore, the role of MHb NR4A2 in cocaine-seeking and relapse behavior remains largely unknown. This is a key open question as NR4A2 is a powerful regulator of memory processes dependent on epigenetic mechanisms. In this study, we examined the role of MHb NR4A2 in cued reinstatement of cocaine self-administration in mice, and found that over-expressing a dominant negative form of Nr4a2 (Nurr2c) in the MHb results in a near complete block of relapse-like behavior. We used single-nucleus transcriptomics to characterize the molecular cascade following the manipulation of Nr4a2, revealing changes in transcriptional networks related to addiction, neuroplasticity, and glutamatergic signaling. Together, these results place the MHb in the reward circuit as a pivotal regulator of relapse behavior and demonstrate the importance of NR4A2 as a key mechanism driving relapse behavior in the MHb.

2024-03-01 | GSE208081 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data