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Stress-induced translation of KCNB1 contributes to the enhanced synaptic transmission of the lateral habenula

ABSTRACT: Stress-induced translation of KCNB1 contributes to the enhanced synaptic transmission of the lateral habenula

PROVIDER: PRJNA1047086 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR27003600_1.fastq.gz	Fastqsanger.gz
	SRR27003600_2.fastq.gz	Fastqsanger.gz
	SRR27003601_1.fastq.gz	Fastqsanger.gz
	SRR27003601_2.fastq.gz	Fastqsanger.gz
	SRR27003602_1.fastq.gz	Fastqsanger.gz

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Stress-induced translation of KCNB1 contributes to the enhanced synaptic transmission of the lateral habenula

Project description:The lateral habenula (LHb) is a well-established brain region involved in depressive disorders. Synaptic transmission of the LHb neurons is known to be enhanced by stress exposure; however, little is known about genetic modulators within the LHb that respond to stress. Using recently developed molecular profiling methods by phosphorylated ribosome capture, we obtained transcriptome profiles of stress responsive LHb neurons during acute physical stress. Among such genes, we found that KCNB1 (Kv2.1 channel), a delayed rectifier and voltage-gated potassium channel, exhibited increased expression following acute stress exposure. To determine the roles of KCNB1 on LHb neurons during stress, we injected short hairpin RNA (shRNA) against the kcnb1 gene to block its expression prior to stress exposure. We observed that the knockdown of KCNB1 altered the basal firing pattern of LHb neurons. Although KCNB1 blockade did not rescue despair-like behaviors in acute learned helplessness (aLH) animals, we found that KCNB1 knockdown prevented the enhancement of synaptic strength in LHb neuron after stress exposure. This study suggests that KCNB1 may contribute to shape stress responses by regulating basal firing patterns and neurotransmission intensity of LHb neurons.

2023-12-05 | GSE249051 | GEO

Acute social isolation alters synaptic plasticity in lateral habenula and social decision

Project description:The lateral habenula (LHb) is an essential hub brain region modulating the monoamine system such as dopamine, serotonin. Hyperactivity of LHb has implications for psychiatric disorders such as depression, anxiety, and schizophrenia, which are commonly associated with social dysfunction. However, the role of LHb in social behavior has remained elusive. Here, we find that experiencing acute social isolation affects synaptic function in LHb and social behavior. After acute social isolation, long-term depression (LTD) in LHb is impaired and rescued by activating the 5-HT4 receptor (5-HT4R). Indeed, Htr4 expression in LHb is up-regulated following acute social isolation. Finally, acute social isolation enhances the social preference for familiars such as housing-mates to stranger conspecifics. Consistent with electrophysiological results, pharmacological activation of 5-HT4R in LHb restored innate social preference. These results suggest that acute social isolation influences social decisions with 5-HT4R-dependent synaptic modification in LHb.

2024-04-30 | GSE200082 | GEO

Acute social isolation alters synaptic plasticity in lateral habenula and social decision

Project description:Acute social isolation alters synaptic plasticity in lateral habenula and social decision

| PRJNA822836 | ENA

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

Chronic stress induces activity, synaptic and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors

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.

2019-09-16 | GSE136723 | 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

Chronic stress induces activity, synaptic and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors

Project description:Chronic stress induces activity, synaptic and transcriptional remodeling of the lateral habenula associated with deficits in motivated behaviors

| PRJNA563337 | ENA

Molecular profiling in the Habenula of Rat Chronic Restaint Stress Model

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.

2022-05-26 | GSE183386 | GEO

Transcriptional profiling of mammalian habenula using scRNAseq

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

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