Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (microRNA)
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ABSTRACT:
ORGANISM(S): Mus musculus synthetic construct
PROVIDER: GSE66452 | GEO | 2015/03/04
SECONDARY ACCESSION(S): PRJNA277005
REPOSITORIES: GEO
Similar Datasets
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
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.
2015-03-04 | GSE66451 | GEO
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
Project description: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.
2020-03-04 | GSE137478 | GEO
Project description:Nicotine contained in tobacco smoke increases blood glucose levels in humans, and the risk of developing diabetes is dramatically increased in habitual smokers. Little is currently known about how nicotine increases blood glucose levels or the relevance of this action to either the persistence of the smoking habit or the pathophysiology of diabetes in smokers. Here, we show that the diabetes-associated gene Tcf7l2 is highly expressed in the medial habenula (mHb), where it regulates the function of local nicotinic acetylcholine receptors. We find that Tcf7l2 mutant (Tcf7l2mut) rats consume far greater quantities of nicotine than wild-type rats. Similarly, CRISPR-mediated cleavage of wild-type Tcf7l2 in the mHb increases nicotine intake in mice. Polysynaptic tracing identified a connection from the mHb to the pancreas, and nicotine-induced activation of the mHb elevates blood glucose. This effect is mimicked by chemogenetic stimulation of the mHb and blocked by Tcf7l2 knockdown in mHb. A history of nicotine consumption elevates circulating levels of the pancreas-derived hormones glucagon and insulin and precipitates diabetes-like dysregulation of blood glucose homeostasis in wild-type rats, whereas Tcf7l2mut rats are resistant to these actions of nicotine. Our findings suggest that Tcf7l2 regulates the stimulatory actions of nicotine on the habenula-pancreas axis, linkings the addictive properties of nicotine to its diabetes-promoting actions.
2019-09-10 | GSE137118 | GEO
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
Project description:Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (mRNA)
| PRJNA277006 | ENA
Project description:Expression data from the Lateral Habenula (LHb) and the Medial Habenula (MHb) of the mouse (C57BL/6) brain after nicotine self-administration (microRNA)
| PRJNA277005 | ENA
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