Regulation of depression-related behaviors by GABAergic neurons in the lateral septum through periaqueductal gray neuronal projections

Wang, Dan; Wang, Wentao; Jiang, Shujun; Ma, He; Lian, Haifeng; Meng, Fantao; Liu, Jing; Cui, Minghu; You, Jungmok; Liu, Cuilan; Zhao, Di; Hu, Fengai; Liu, Dunjiang; Li, Chen

doi:10.1016/j.jpsychires.2021.02.043

Cited by 23 publications

(19 citation statements)

References 58 publications

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“…Additionally, neither chronic stress nor quinine treatment produced an impact on the locomotor activity and anxious status of mice in OFT (Figure 3 ), indicating that chronic stress or quinine treatment made no difference to the excitability of central nervous system, which was consistent with other studies (Frisch et al., 2005 ; Su et al., 2018 ). In a recent study, neither 5 weeks nor 9 weeks of CUMS changed the locomotor activity of mice in OFT (Wang et al., 2021 ). As to quinine, similar results showed that knockout of Cx36 did not affect the locomotor activity of mice in OFT (Frisch et al., 2005 ; Steffensen et al., 2011 ).…”

Section: Discussionmentioning

confidence: 92%

“…Both clinical and experimental evidence showed that the emotional circuits associated with depressive disorder consisted of different parts of the brian, such as PFC, ventral hippocampus, amygdala and nucleus accumbens (Nac) (Wang, Wang et al., 2021 ). In our study, we found the increase of Cx36 induced by chronic stress mainly appeared in the hippocampus, but not PFC.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

Jiang

Zeng

et al. 2022

Brain and Behavior

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Background: High mobility group box 1 (HMGB1) released by neurons and microglia was demonstrated to be an important mediator in depressive-like behaviors induced by chronic unpredictable mild stress (CUMS), which could lead to the imbalance of two different metabolic approaches in kynurenine pathway (KP), thus enhancing glutamate transmission and exacerbating depressive-like behaviors. Evidence showed that HMGB1 signaling might be regulated by Connexin (Cx) 36 in inflammatory diseases of central nervous system (CNS). Our study aimed to further explore the role of Cx36 in depressive-like behaviors and its relationship with HMGB1.Methods: After 4-week chronic stress, behavioral tests were conducted to evaluate depressive-like behaviors, including sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), and open field test (OFT). Western blot analysis and immunofluorescence staining were used to observe the expression and location of Cx36. Enzyme-linked immunosorbent assay (ELISA) was adopted to detect the concentrations of inflammatory cytokines. And the excitability and inward currents of hippocampal neurons were recorded by whole-cell patch clamping. Results:The expression of Cx36 was significantly increased in hippocampal neurons of mice exposed to CUMS, while treatment with glycyrrhizinic acid (GZA) or quinine could both down-regulate Cx36 and alleviate depressive-like behaviors. The proinflammatory cytokines like HMGB1, tumor necrosis factor alpha (TNF-α), and interleukin-1β (IL-1β) were all elevated by CUMS, and application of GZA and quinine could decrease them. In addition, the enhanced excitability and inward currents of hippocampal neurons induced by lipopolysaccharide (LPS) could be reduced by either GZA or quinine.Conclusions: Inhibition of Cx36 in hippocampal neurons might attenuates HMGB1mediated depressive-like behaviors induced by CUMS through down-regulation of the proinflammatory cytokines and reduction of the excitability and intracellular ion overload.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

Jiang

Zeng

et al. 2022

Brain and Behavior

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“…The septum is an evolutionarily conserved part of the limbic system that has diverse functions in regulating emotional states and behavioral responses, such as anxiety, locomotion, feeding, and sociality [ 12 , 14 , 83 ]. Previous studies suggest that the lateral septum is associated with depression [ 63 , 84 , 85 ], but the underlying neural substrates are less well-understood. Our results presented here show that SST neurons in the LS contribute to the regulation of depressive-like behaviors in mice.…”

Section: Discussionmentioning

confidence: 99%

“…A recent study shows that vesicular GABA transporter (VGAT)-positive GABAergic neurons in the LS exhibit increased c-Fos activation after chronic unpredictable stress. Activation of LS GABA neurons and their projections to the periaqueductal gray increase depressive-like behaviors, while inhibiting this LS GABA circuit reduces depression phenotypes in mice [ 63 ]. Our results that activation of LS SST neurons alleviates depressive-like behaviors are not contradictory to the findings of Wang et al (2021) due to the heterogeneity and complexity of neuronal subtypes.…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies have shown that antidepressant drugs can increase LS neural activity [ 59 , 60 , 61 , 62 ]. A recent study shows that LS GABAergic (LS GABA ) neurons regulate depression-related behaviors through their projections to the periaqueductal gray [ 63 ]. However, it is unclear how different neuronal subpopulations of the LS GABA neurons contribute to depression regulation.…”

Section: Introductionmentioning

confidence: 99%

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Activation of Somatostatin-Expressing Neurons in the Lateral Septum Improves Stress-Induced Depressive-like Behaviors in Mice

Sung

Lau

2022

Pharmaceutics

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Depression is a debilitating mood disorder with highly heterogeneous pathogenesis. The limbic system is well-linked to depression. As an important node in the limbic system, the lateral septum (LS) can modulate multiple affective and motivational behaviors. However, the role of LS in depression remains unclear. By using c-Fos expression mapping, we first screened and showed activation of the LS in various depression-related behavioral tests, including the forced swim test (FST), tail suspension test (TST), and sucrose preference test. In the LS, more than 10% of the activated neurons were somatostatin-expressing (SST) neurons. We next developed a microendoscopic calcium imaging method in freely moving mice and revealed that LSSST neural activity increased during mobility in the TST but not open field test. We hypothesize that LSSST neuronal activity is linked to stress and depression. In two mouse models of depression, repeated lipopolysaccharide (LPS) injection and chronic restraint stress (CRS), we showed that LS neuronal activation was suppressed. To examine whether the re-activation of LSSST neurons can be therapeutically beneficial, we optogenetically activated LSSST neurons and produced antidepressant-like effects in LPS-injected mice by increasing TST motility. Moreover, chemogenetic activation of LSSST neurons increased FST struggling in the CRS-exposed mice. Together, these results provide the first evidence of a role for LSSST neurons in regulating depressive-like behaviors in mice and identify them as a potential therapeutic target for neuromodulation-based intervention in depression.

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Behavioral Animal Models and Neural-Circuit Framework of Depressive Disorder

Tian,

Russo,

2024

Neurosci. Bull.

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Depressive disorder is a chronic, recurring, and potentially life-endangering neuropsychiatric disease. According to a report by the World Health Organization, the global population suffering from depression is experiencing a significant annual increase. Despite its prevalence and considerable impact on people, little is known about its pathogenesis. One major reason is the scarcity of reliable animal models due to the absence of consensus on the pathology and etiology of depression. Furthermore, the neural circuit mechanism of depression induced by various factors is particularly complex. Considering the variability in depressive behavior patterns and neurobiological mechanisms among different animal models of depression, a comparison between the neural circuits of depression induced by various factors is essential for its treatment. In this review, we mainly summarize the most widely used behavioral animal models and neural circuits under different triggers of depression, aiming to provide a theoretical basis for depression prevention.

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Regulation of depression-related behaviors by GABAergic neurons in the lateral septum through periaqueductal gray neuronal projections

Cited by 23 publications

References 58 publications

Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

Inhibition of Connexin 36 attenuates HMGB1‐mediated depressive‐like behaviors induced by chronic unpredictable mild stress

Activation of Somatostatin-Expressing Neurons in the Lateral Septum Improves Stress-Induced Depressive-like Behaviors in Mice

Behavioral Animal Models and Neural-Circuit Framework of Depressive Disorder

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