Identification of the subventricular tegmental nucleus as brainstem reward center

Science, Journal Year: 2025, Volume and Issue: 387(6732)

Published: Jan. 23, 2025

Rewards are essential for motivation, decision-making, memory, and mental health. We identified the subventricular tegmental nucleus (SVTg) as a brainstem reward center. In mice, its prediction activate SVTg, SVTg stimulation leads to place preference, reduced anxiety, accumbal dopamine release. Mice self-stimulate which can also be activated directly by neocortex, resulting in effective inhibition of lateral habenula, region associated with depression. This mechanism may explain why suppression induces aversion increases fear. The translational relevance these findings is supported evidence rat, monkey, human brainstem, establishing key hub processing, emotional valence, motivation.

Language: Английский

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The thalamic reticular nucleus-lateral habenula circuit regulates depressive-like behaviors in chronic stress and chronic pain

Cell Reports, Journal Year: 2023, Volume and Issue: 42(10), P. 113170 - 113170

Published: Sept. 21, 2023

Chronic stress and chronic pain are two major predisposing factors to trigger depression. Enhanced excitatory input the lateral habenula (LHb) has been implicated in pathophysiology of However, contribution inhibitory transmission remains unclear. Here, we dissect an projection from sensory thalamic reticular nucleus (sTRN) LHb, which is activated by acute aversive stimuli. restraint (CRS) weakens sTRN-LHb synaptic strength, this attenuation indispensable for CRS-induced LHb neural hyperactivity depression onset. Moreover, artificially inhibiting circuit induces depressive-like behaviors healthy mice, while enhancing relieves induced both pain. Intriguingly, neither neuropathic nor comorbid mechanical hypersensitivity affected pathway. Altogether, our study demonstrates establishing modulating depression, thus shedding light on potential therapeutic targets preventing or managing

Language: Английский

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The lateral habenula: A hub for value-guided behavior

Cell Reports, Journal Year: 2024, Volume and Issue: 43(4), P. 113968 - 113968

Published: March 22, 2024

SummaryThe habenula is an evolutionarily highly conserved diencephalic brain region divided into two major parts, medial and lateral. Over the past decades, studies of lateral (LHb), in particular, have identified key functions value-guided behavior health disease. In this review, we focus on recent insights LHb connectivity its functional relevance for different types aversive appetitive behavior. First, give overview anatomical organization main cellular composition. Next, elaborate how distinct neuronal subpopulations encode stimuli their involvement more complex decision-making processes. Finally, scrutinize afferent efferent connections discuss implications LHb-dependent A deepened understanding circuit components will substantially contribute to our knowledge

Language: Английский

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Deep brain stimulation in the lateral habenula reverses local neuronal hyperactivity and ameliorates depression-like behaviors in rats

Neurobiology of Disease, Journal Year: 2023, Volume and Issue: 180, P. 106069 - 106069

Published: March 7, 2023

Deep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major suggests that LHb might be effective target of DBS depression. Here, we found in effectively decreased depression-like behaviors rats experienced with chronic unpredictable mild stress (CUMS), well-accepted paradigm modeling depression rodents. In vivo electrophysiological recording unveiled CUMS increased neuronal burst firing, as well proportion neurons showing hyperactivity to aversive stimuli LHb. Nevertheless, downregulated local field potential power, reversed CUMS-induced increase firing stimuli, coherence ventral tegmental area (VTA). Our results demonstrate exerts antidepressant-like reverses neural hyperactivity, supporting

Language: Английский

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A potentiation of REM sleep-active neurons in the lateral habenula may be responsible for the sleep disturbance in depression

Current Biology, Journal Year: 2024, Volume and Issue: 34(15), P. 3287 - 3300.e6

Published: June 28, 2024

Language: Английский

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Quantitative and qualitative sex difference in habenula-induced inhibition of midbrain dopamine neurons in the rat

Frontiers in Behavioral Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Nov. 13, 2023

Introduction Clinically relevant sex differences have been noted in a number of affective, behavioral, cognitive, and neurological health disorders. Midbrain dopamine neurons are implicated several these same disorders consequently under investigation for their potential role the manifestation differences. The lateral habenula exerts significant inhibitory control over neuronal firing, yet little is known about this particular neurocircuit. Methods We performed vivo , single unit, extracellular recordings female male anesthetized rats response to pulse stimulation habenula. In addition, we assessed baseline firing properties and, by immunochemical means, distribution estrogen receptor alpha cells Results Habenula-induced inhibition reduced relative rats. had higher prevalence rebound excitation. Furthermore, pattern was less variable rats, density positive Discussion found that habenular both qualitatively quantitatively different These novel findings together with reports contemporary literature lead us posit difference seen here relate differential resulting from presence hormones. Further work needed test hypothesis, which may implications understanding etiology mental including depression, schizophrenia, addiction.

Language: Английский

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Comprehensive Brain-wide Mapping of Afferent and Efferent Nuclei Associated with the Heart in the Mouse

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: March 15, 2025

Language: Английский

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Sexually Dimorphic Cellular Architecture and Neural Circuity of ovBNST Proenkephalin Neurons

Neuroscience Bulletin, Journal Year: 2025, Volume and Issue: unknown

Published: May 30, 2025

Language: Английский

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Whole-brain connections of glutamatergic neurons in the mouse lateral habenula in both sexes

Biology of Sex Differences, Journal Year: 2024, Volume and Issue: 15(1)

Published: April 23, 2024

Abstract Background The lateral habenula (LHb) is an epithalamus nucleus that evolutionarily conserved and involved in various physiological functions, such as encoding value signals, integrating emotional information, regulating related behaviors. cells the LHb are predominantly glutamatergic have heterogeneous functions response to different stimuli. circuitry connections of neurons play a crucial role wide range events. However, both sexes not been thoroughly investigated. Methods In this study, we injected Cre-dependent retrograde trace virus anterograde synaptophysin-labeling into adult male female Vglut2-ires-Cre mice, respectively. We then quantitatively analyzed input output ipsilateral contralateral whole brain. Results Our findings showed inputs vGlut2 come from more than 30 brain subregions, including cortex, striatum, pallidum, thalamus, hypothalamus, midbrain, pons, medulla, cerebellum with no significant differences between males females. outputs targeted eight large regions, primarily focusing on midbrain pons nuclei, distinct features presynaptic bouton across subregions. While correlation cluster analysis revealed collateral projection features, input-output connection pattern was highly similar. Conclusions This study provides systematic comprehensive shedding light anatomical architecture these specific cell types mouse LHb. structural understanding can help guide further investigations complex

Language: Английский

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The disappointment centre of the brain gets exciting: a systematic review of habenula dysfunction in depression

Translational Psychiatry, Journal Year: 2024, Volume and Issue: 14(1)

Published: Dec. 19, 2024

The habenula is an epithalamic brain structure that acts as a neuroanatomical hub connecting the limbic forebrain to major monoamine centres. Abnormal activity increasingly implicated in depression, with surge publications on this topic last 5 years. Direct activation of sufficient induce depressive phenotype rodents, suggesting causative role depression. However, molecular basis dysfunction depression remains elusive and it unclear how preclinical advancements translate clinical field. A systematic literature search was conducted following PRISMA guidelines. two terms depress* habenula* were applied across Scopus, Web Science PubMed databases. Studies eligible for inclusion must have examined cases or models compared their measures appropriate control. Preclinical studies (n = 63) measured markers 16) neuronal firing 22), largely implicating hyperactivity Neurotransmission briefly explored 15), imbalances within excitatory inhibitory signalling. Additional reported neuroconnectivity 1), inflammatory 3), genomic 3) circadian rhythm abnormalities. Seven (11%) included both males females. From these, (71%) significant difference between sexes at least one measure taken. Clinical 24) abnormalities connectivity volume 6) 3). generally male female subjects 16), however, few these sex biological variable 6). Both evidence suggest disrupted there are opportunities sex-specific analyses areas. consistently suggests primary driver development symptoms. support gross such altered activation, connectivity, volume, emerging blood barrier dysfunction, progress limited by lack detailed imaging resolution.

Language: Английский

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