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

Zhang, Yuqi; Ma, Longyu; Zhang, Xueying; Yue, Lupeng; Wang, Jiaxin; Zheng, Jie; Cui, Shuang; Liu, Fengyu; Wang, Zhiyan; Wan, You; Yi, Ming

doi:10.1016/j.nbd.2023.106069

Cited by 11 publications

(6 citation statements)

References 57 publications

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“…In rodents, a study measured LFPs in the LHb before and after a DBS protocol. In this study, PSD was lower after the DBS from theta to low gamma frequencies (Zhang et al, 2023). Because DBS reduced depressive symptoms, this suggests that lower PSD in these frequencies was associated with a decrease in depressive symptoms.…”

Section: Is the Habenula Hyperactive In Human Depression?supporting

confidence: 48%

“…There is indeed evidence that the rapid antidepressant effect of ketamine is elicited by reversing the increased burst firing of LHb neurons (Yang, Cui et al, 2018). Likewise, deep brain stimulation (DBS) of the LHb, which has been shown to alleviate symptoms of depression in rodents (e.g., Akhoondian et al, 2023;Meng et al, 2011), also appears to exert its effect by reversing the increased burst firing of LHb neurons (Zhang et al, 2023). In essence, the above literature highlights hyperactivity of the LHb as a core neural mechanism driving depression.…”

Section: Introductionmentioning

confidence: 99%

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The Habenula in Mood Disorders: A Scoping Review of Human Studies

Fortin,

Lafleur,

Parisien

et al. 2024

Preprint

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In animal models, the habenula has been identified as a key structure involved in depression. Thanks to recent technological advancements, a burgeoning body of work has also investigated the habenula in the context of human mood disorders. This scoping review aims to synthesize findings from human studies that pertain to the habenula and its relationship with mood disorders. The review was conducted according to PRISMA guidelines. The literature search was performed with PubMed and yielded 93 articles, of which 50 articles were included in the review. We found that the evidence for baseline habenular hyperactivity in human depression is mixed. As for findings from resting-state functional connectivity (RSFC) studies, they were mainly inconsistent across studies. Moreover, we found no evidence indicating that mood disorders are linked to changes in the volume of the habenula. In order to enhance the replicability of findings, given the small size of the habenula, higher image resolution and larger samples are recommended for future studies.

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Section: Is the Habenula Hyperactive In Human Depression?supporting

confidence: 48%

Section: Introductionmentioning

confidence: 99%

The Habenula in Mood Disorders: A Scoping Review of Human Studies

Fortin,

Lafleur,

Parisien

et al. 2024

Preprint

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“…Rather than abnormal tonic firing, the dysregulated Hb neuronal activity appears to be specific to a subtype of burst neurons. Greater spontaneous bursting activity in the LHb has been reported following chronic (n=7), acute (n=1) and early life stress paradigms (n=3) (42, 50, 52, 62, 51, 61, 75, 84). Similarly, this phenomenon has been observed in the genetic congenitally learned helplessness model (n=2) (72, 79) and in an inflammatory model of depression (42).…”

Section: Resultsmentioning

confidence: 97%

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

Cameron,

Weston-Green,

Newell

2024

Preprint

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Background: The habenula is an epithalamic brain structure that acts as a neuroanatomical hub connecting the limbic forebrain to the major monoamine centres. Abnormal habenula activity is increasingly implicated in depression, with a surge in publications on this topic in the last 5 years. Direct stimulation of the habenula is sufficient to induce a depressive phenotype in rodents, suggesting a causative role in depression. However, the molecular basis of habenula dysfunction in depression remains elusive and it is unclear how the preclinical advancements translate to the clinical field. Methods: A systematic literature search was conducted following the PRISMA guidelines. The two search terms depress* and habenula* were applied across the databases Scopus, Web of Science and PubMed. Studies eligible for inclusion must have examined changes in the habenula in clinical cases of depression or preclinical models of depression. Results: Preclinical studies (n=57) measured markers of habenula activity (n=16) and neuronal firing (n=21), largely implicating habenula hyperactivity in depression. Neurotransmission was briefly explored (n=13), suggesting imbalances within excitatory and inhibitory habenula signalling. Additional preclinical studies reported neuroconnectivity (n=1), inflammatory (n=2), genomic (n=2) and circadian rhythm (n=2) abnormalities. Seven preclinical studies (12.2%) included both males and females. From these, 5 studies (71%) reported a significant difference between the sexes in at least one habenula measure taken. Clinical studies (n=18) reported abnormalities in habenula connectivity (n=11), volume (n=5) and molecular markers (n=2). Clinical studies generally included male and female subjects (n=15), however, few of these studies examined sex as a biological variable (n=5) Conclusions: Both preclinical and clinical evidence suggest the habenula is disrupted in depression. However, there are opportunities for sex-specific analyses across both areas. Preclinical evidence consistently suggests habenula hyperactivity as a primary driver for the development of depressive symptoms. Clinical studies support gross habenula abnormalities such as altered activation, connectivity, and volume, with emerging evidence of blood brain barrier dysfunction, however, progress is limited by a lack of detailed molecular analyses.

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“…44 Additionally, research has demonstrated that deep brain stimulation can reverse the progression of depression-like characteristics in rats through changes in LHb-VTA circuit connections. 45 Similarly, in depressed mice with nerve cuffing injury, LHb glutamatergic neurons exhibit the highest spike firing rate. Activating the LHb Glu -VTA GABA-DA circuit using chemogenetic and optogenetic methods can trigger depressive-like behaviors and worsen pain.…”

Section: ■ Neural Circuitsmentioning

confidence: 99%

Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment

Zhang,

Ma,

Bai

et al. 2024

ACS Chem. Neurosci.

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Chronic neuropathic pain and comorbid depression syndrome (CDS) is a major worldwide health problem that affects the quality of life of patients and imposes a tremendous socioeconomic burden. More than half of patients with chronic neuropathic pain also suffer from moderate or severe depression. Due to the complex pathogenesis of CDS, there are no effective therapeutic drugs available. The lack of research on the neural circuit mechanisms of CDS limits the development of treatments. The purpose of this article is to provide an overview of the various circuits involved in CDS. Notably, activating some neural circuits can alleviate pain and/or depression, while activating other circuits can exacerbate these conditions. Moreover, we discuss current and emerging pharmacotherapies for CDS, such as ketamine. Understanding the circuit mechanisms of CDS may provide clues for the development of novel drug treatments for improved CDS management.

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

Cited by 11 publications

References 57 publications

The Habenula in Mood Disorders: A Scoping Review of Human Studies

The Habenula in Mood Disorders: A Scoping Review of Human Studies

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

Chronic Neuropathic Pain and Comorbid Depression Syndrome: From Neural Circuit Mechanisms to Treatment

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