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

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

PROVIDER: PRJNA563337 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR10056200_1.fastq.gz	Fastqsanger.gz
	SRR10056200_2.fastq.gz	Fastqsanger.gz
	SRR10056201_1.fastq.gz	Fastqsanger.gz
	SRR10056201_2.fastq.gz	Fastqsanger.gz
	SRR10056202_1.fastq.gz	Fastqsanger.gz

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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

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

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Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors

Project description:Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors

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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

Hyperactive lateral habenula mediates the comorbidity between rheumatoid arthritis and depression-like behaviors

Project description:Objective: The aim of this study was to identify the neural and molecular mechanisms underlying the comorbidity of rheumatoid arthritis (RA) and depression. Methods: A cohort of 200 RA patients were recruited to quantitatively assess the association between depressive symptoms and RA disease activity, as well as quality of life. The collagen antibody-induced arthritis (CAIA) mouse model of RA was used to screen for brain regions that showed changes in c-FOS expression, an indicator of alteration in brain activity, accompanying the appearance of depression-like behaviors. RNA sequencing, immunostaining, AAV-mediated expression, micro-CT, plasma cytokines/chemokines measurements and histological analyses were applied to evaluate the contribution of the identified brain region in the disease progression of RA and depression-like symptoms. Results: In this study, we showed that in RA patients, the depression scores were significantly correlated with the severity and quality of life of the patients. The CAIA mice developed RA symptoms, together with depression-like behaviors accompanied by hyperactivity and alterations in gene expression reflecting cerebrovascular disruption in the lateral habenula (LHb), a brain region processing negative valence. Importantly, inhibition of the LHb outputs not only alleviated depression-like behaviors, but also resulted in rapid remission of RA symptoms and reduction in sympathetic nerve fibers in the synovial joints of the CAIA mice.Conclusion: Our study highlights a critical but previously overlooked contribution of hyperactive LHb to the comorbidity between RA and depression, suggesting that targeting LHb in conjunction with RA treatments may be a promising strategy for RA patients comorbid with depression.

2025-08-30 | GSE241929 | GEO

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

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

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Activation of proprotein convertase in the mouse habenula causes depressive-like behaviors through remodeling of extracellular matrix

Project description:We performed RNA-seq in lateral habenula of mice with susceptibility to chronic social defeat stress.

2020-08-28 | GSE156965 | 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