Project description:Chronic stressful situations contribute to the risk of developing depression. Using Genome-wide gene expression analysis, we analyzed the habenula transcriptome of rats exposed to chronic restraint stress for 14 days. We selected 379 differentially expressed genes (DEGs) affected by chronic stress. From 379 DEGs, neuroactive ligand-receptor interaction, cAMP signaling pathway, circadian entrainment and synaptic signaling on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, response to corticosteroid, positive regulation of lipid transport, anterograde trans-synaptic signaling, chemical synapse transmission on Gene Ontology (GO) pathway analysis was identified as significantly enriched pathways. We made a protein-protein interaction network of DEGs and analyzed subclusters, and neuroactive ligand-receptor interaction, circadian entrainment, and cholinergic synapse-related clusters were identified. To validate the findings, quantitative RT-PCR was done for significant genes. Identified DEGs and pathways could be important factors modulating habenular response to stress and lead to behavioral change. These data identify key molecular targets involved in chronic stress-induced depression within habenula and provides a valuable resource for future study.
Project description:We report changes in molecular profile in rat lateral habenula in response to chronic mild stress, and than in response to antidepressant treatment.
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.
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.
Project description:Chronic stress (CMS) affects many brain functions and is a major risk factor for the development of depression. Here, we demonstrate that CMS-induced hyperactivity in VTA-projecting lateral habenula (LHb) neurons is associated with increased passive coping (PC) but not anxiety or anhedonia. LHb→VTA neurons in mice with increased PC show increased burst and tonic firing as well as synaptic adaptations in excitatory inputs from the entopeduncular nucleus (EP). In-vivo manipulations of EP→LHb or LHb→VTA neurons selectively alter PC and effort-related motivation. Conversely, dorsal raphe (DR)-projecting LHb neurons do not show CMS-induced hyperactivity and are targeted indirectly by the EP. Using single-cell transcriptomics we reveal a set of genes that can collectively serve as biomarkers to identify mice with increased PC and differentiate LHb→VTA from LHb→DR neurons. Together, we provide a set of biological markers at the level of genes, synapses, cells and circuits that define a distinctive CMS-induced behavioral phenotype.
Project description:Here, we examine behavioral and brain transcriptomic (RNA-seq) responses in rat prolonged chronic unpredictable stress (PCUS) model, and their modulation by 4-week treatment with fluoxetine, eicosapentaenoic acid (EPA), lipopolysaccharide (LPS) and their combinations.