Distinct projections from the infralimbic cortex exert opposing effects in modulating anxiety and fear

Chen, Yihua; Wu, Jianlin; Hu, Nan; Zhuang, Jia-Pai; Li, Weipeng; Zhang, Sheng-Rong; Li, Xiaowen; Yang, Jian‐Ming; Gao, Tianming

doi:10.1172/jci145692

Cited by 79 publications

(58 citation statements)

References 81 publications

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“…Macrophage is one of the most important effector cells in silicosis, which is continuously activated via silica stimulation, secreting multiple inflammatory factors and exacerbating silicosis [ 13 ]. Macrophages play a crucial role in the progression of pulmonary fibrosis by triggering the inflammation cascade response and differentiating into a profibrotic phenotype [ 14 , 15 ]. Silica damages the epithelial cell and also activates the macrophage to cause an inflammatory microenvironment in the lung, which promotes adaptive immunity, fibroblast proliferation and migration, extracellular matrix secretion and collagen deposition, eventually leading to abnormal lung tissue remodeling and obstructive air exchange, even death [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

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Background Silicosis is one of the most common occupational pulmonary fibrosis caused by respirable silica-based particle exposure, with no ideal drugs at present. Metformin, a commonly used biguanide antidiabetic agent, could activate AMP-activated protein kinase (AMPK) to exert its pharmacological action. Therefore, we sought to investigate the role of metformin in silica-induced lung fibrosis. Methods The anti-fibrotic role of metformin was assessed in 50 mg/kg silica-induced lung fibrosis model. Silicon dioxide (SiO2)-stimulated lung epithelial cells/macrophages and transforming growth factor-beta 1 (TGF-β1)-induced differentiated lung fibroblasts were used for in vitro models. Results At the concentration of 300 mg/kg in the mouse model, metformin significantly reduced lung inflammation and fibrosis in SiO2-instilled mice at the early and late fibrotic stages. Besides, metformin (range 2–10 mM) reversed SiO2-induced cell toxicity, oxidative stress, and epithelial-mesenchymal transition process in epithelial cells (A549 and HBE), inhibited inflammation response in macrophages (THP-1), and alleviated TGF-β1-stimulated fibroblast activation in lung fibroblasts (MRC-5) via an AMPK-dependent pathway. Conclusions In this study, we identified that metformin might be a potential drug for silicosis treatment.

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Section: Introductionmentioning

confidence: 99%

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Cheng

Wang

et al. 2021

J Transl Med

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“…In addition, the regulation of sociability by mPFC-PV + interneurons found in prior studies ( Bicks et al, 2020 ) can corroborate the positive and negative impacts on social preference when we modify IL-PV + interneurons. Moreover, the distinct IL outputs showed completely opposite effects of anxiety regulation, as the IL to the lateral septum (LS) projections promote anxiety whereas the IL to the central nucleus of the amygdala (CeA) projections exert anxiolytic activity ( Chen et al, 2021 ); this may also explain our findings that activation of IL-PV + interneurons is able to rescue anxiety, but inhibition of the IL is not sufficient to increase anxiety, suggesting that other mechanisms may still have a synchronous effect in the control of anxiety-like behaviors.…”

Section: Discussionmentioning

confidence: 99%

Dysregulation of prefrontal parvalbumin interneurons leads to adult aggression induced by social isolation stress during adolescence

Sun

Zhu

et al. 2022

Front. Mol. Neurosci.

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Social isolation during the juvenile stage results in structural and functional impairment of the brain and deviant adult aggression. However, the specific subregions and cell types that underpin this deviant behavior are still largely unknown. Here, we found that adolescent social isolation led to a shortened latency to attack onset and extended the average attack time, accompanied by anxiety-like behavior and deficits in social preference in adult mice. However, when exposed to social isolation during adulthood, the mice did not show these phenotypes. We also found that the structural plasticity of prefrontal pyramidal neurons, including the dendritic complexity and spine ratio, was impaired in mice exposed to adolescent social isolation. The parvalbumin (PV) interneurons in the prefrontal infralimbic cortex (IL) are highly vulnerable to juvenile social isolation and exhibit decreased cell numbers and reduced activation in adulthood. Moreover, chemogenetic inactivation of IL-PV interneurons can mimic juvenile social isolation-induced deviant aggression and social preference. Conversely, artificial activation of IL-PV interneurons significantly attenuated deviant aggression and rescued social preference during adulthood in mice exposed to adolescent social isolation. These findings implicate juvenile social isolation-induced damage to IL-PV interneurons in long-term aggressive behavior in adulthood.

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“…Functional differences among anatomically distinct L5 neuronal subpopulations have been reported in sensory (44, 45), frontal/motor (46, 47), prefrontal (48, 49), and anterior cingulate (50) cortices of rodents. The anatomical and functional heterogeneity in L5 neurons of the insula, however, remains poorly understood, despite the wide variety of subcortical efferents of the insula and their difference between A-P subregions (2, 19, 21, 23).…”

Section: Discussionmentioning

confidence: 99%

Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive behavior

Takemoto

Kato

Kobayashi

et al. 2022

Preprint

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The insular cortex (insula) is known to play a modulatory role in feeding. Despite its unique laminar cytoarchitecture, the contribution of each layer of the insula to the behavioral modulation remains elusive. Here, we show that layer 5 of the mouse dysgranular insula has distinct neuronal subpopulations: the upper layer (L5a) population projects bilaterally to the lateral and capsular divisions of the central amygdala, and the deeper layer (L5b) population projects ipsilaterally to the parasubthalamic nucleus and the medial division of the central amygdala. Optogenetically activating L5a and L5b neuronal populations in thirsty mice led to suppressed and facilitated water spout licking, respectively, in a single-spout test, and induced no avoidance against or preference for the spout paired with the opto-activation in a two-spout choice test. Our results suggest sublayer-specific bidirectional modulatory roles of insula layer 5 in the motivational aspect of appetitive behavior.TeaserDistinct sublayers of layer 5 of the insula modulate the motivational aspect of appetitive behavior in an opposite way.

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Distinct projections from the infralimbic cortex exert opposing effects in modulating anxiety and fear

Cited by 79 publications

References 81 publications

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling

Dysregulation of prefrontal parvalbumin interneurons leads to adult aggression induced by social isolation stress during adolescence

Dissection of insular cortex layer 5 reveals two sublayers with opposing modulatory roles in appetitive behavior

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