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Association of Increased Amygdala Activity with Stress-Induced Anxiety but not Social Avoidance Behavior in Mice

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Neuroscience Bulletin 2022年第1期38卷 16-28页

作者： Shou-He Huang Wei-Zhu Liu Xia Qin Chen-Yi Guo Qing-Cheng Xiong Yu Wang Ping Hu bing-xing pan Wen-Hua Zhang Laboratory of Fear and Anxiety Disorders Institutes of Life ScienceNanchang UniversityNanchang330031China Institute of Translational Medicine Nanchang UniversityNanchang330001China

Chronic stress leads to many psychiatric disorders,including social and anxiety disorders that are associated with over-activation of neurons in the basolateral amygdala(BLA).However,not all individuals develop psychiatric diseases,many showing considerable resilience against stress *** BLA neuronal activity is involved in regulating an individual’s vulnerability to stress remains *** this study,using a mouse model of chronic social defeat stress(CSDS),we divided the mice into susceptible and resilient subgroups based on their social interaction *** in vivo fiber photometry and in vitro patch-clamp recording,we showed that CSDS persistently(after 20 days of recovery from stress)increased BLA neuronal activity in all the mice regardless of their susceptible or resilient nature,although impaired social interaction behavior was only observed in susceptible *** anxiety-like behavior,on the other hand,was evident in both ***,the CSDS-induced increase of BLA neuronal activity correlated well with the heightened anxiety-like but not the social avoidance behavior in *** findings provide new insight to our understanding of the role of neuronal activity in the amygdala in mediating stress-related psychiatric disorders.

关键词： Chronic stress Amygdala Stress vulnerability Anxiety Fiber photometry Neuronal activity

Chronic stress causes projection-specific adaptation of amygdala neurons via SK channel downregulation

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Chronic stress causes projection-specific adaptation of amyg...

2019中国生理学会学术年会暨张锡钧基金第十五届全国青年优秀生理学学术论文交流会及第十三届全国青年生理学工作者学术会议

作者：张文华 bing-xing pan Nanchang University

The role of the amygdala in mediating stress-coping has been long ***,basolateral amygdala projection neurons (BLA PNs) are organized into discrete outputs circuits and it remains unclear whether stress differentially impacts these *** were exposed to acute or chronic restraint stress (CRS) and c-fos expression was measured, as a proxy for neuronl activation, in (Retrobead retrogradely-labeled) dorsomedial

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Chronic stress suppresses tonic inhibitory currents via activation of glucocorticoid receptors

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Chronic stress suppresses tonic inhibitory currents via acti...

中国神经科学学会第十届全国学术会议

作者： Min WANG Zhi-Peng LIU bing-xing pan Institute of Life Science Nanchang University

As a key part of the limbic system in the mammalian brain,the amygdala complex plays an essential role in the generation and expression of emotion such as fear and *** generally known,chronic stress exposure leads to the overexcitation of the projection neurons in amygdala,resulting in long-lasting and inappropriate expression of ***,the underpinning neurobiological mechanisms remain largely ***,we made two mice models to mimic the chronic stress exposure in reality-chronic immobilization stress and chronic unpredictable *** using the whole-cell configuration of patch clamp in amygdala slices,we investigate the possible influence of chronic stress on the inhibitory current in the projection neurons in *** find both forms of chronic stress conspicuously decrease the tonic inhibitory currents in the PNs,which are mediated by the GABA receptors in extrasynaptic *** contrast,they have only negligible effect on the phasic inhibitory currents mediated by the postsynaptic GABA *** effect is dependent on the time course of chronic immobilization *** CIS for 8-10 days significantly compromise the tonic inhibitory currents in PNs,CIS for 4-6 days had only slight but insignificant influence on tonic *** study demonstrates that the CIS-evoked loss of tonic inhibitory current was primarily mediated by glucocorticoid *** the mice with 5μM corticosterone mimics the effect of chronic stress on tonic inhibition and strikingly suppresses the tonic inhibitory currents in amygdala ***,treatment of the CIS mice with glucocorticoid receptor antagonist RU 38486 completely reversed the loss of tonic inhibitory *** contrast,mineralocorticoid receptor antagonist Spironolactone had no effect on the decreased tonic ***,our study offers important experimental evidence to unveil the neurobiological basis underlying the action of CIS on amygdala and provides potential target

关键词： amygdala chronic stress tonic inhibition neuron glucocorticoid receptors

Amygdala neurons in face of chronic stress: projection-specific adaptation and its relevance to subsequent to anxiogesis

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Amygdala neurons in face of chronic stress: projection-speci...

中国神经科学学会第十二届全国学术会议

作者： Wen-Hua Zhang Wei-Zhu Liu Jun-Yu Zhang Tao-Hui Liu bing-xing pan Institute of Life Science Nanchang University

Prolonged activation of the projection neurons in amygdala contributes to the development of anxiety and mood disorders related to chronic stress exposure. Although these neurons are anatomically intermingled, recent studies have revealed that they are integrated into different functional circuits and thus have divergent roles in amygdalarelated behaviors. It remains unclear how chronic stress recruits these amygdala neurons to mediate its adversity on emotion. By using retrograde tracing, immunohistochemistry and electrophysiology, we explored the modulation of diverse forms of stress on mice basal amygdala（BA） neurons projecting either to medial prefrontal cortex or elsewhere（designated as BA-mPFC and non-BA-mPFC neurons respectively）. We first observed that the vast majority of BA-mPFC neurons were architecturally segregated from the nonBA-mPFC neurons. While exhibiting similar activation and recovery upon acute immobilization stress, these two neuronal subsets showed sharply diverse pattern of adaptation to chronic stress（CIS）. Specifically, CIS persistently increased the expression of c-fos, an early immediate gene, in the non-BA-mPFC neurons but left that unaltered in BA-mPFC neurons, suggesting neuron-specific recruitment. Such specificity was paralleled by enhanced intrinsic excitability with reduced expression of SK channel currents in the non-BA-mPFC but not BA-mPFC neurons. Importantly, CIS-induced anxiogesis was closely associated with the loss of AHP currents in their non-BA-mPFC neurons. Our findings suggest that chronic stress preferentially recruit non-BA-mPFC neurons to have its adversity on emotion. Targeted suppression of these neurons may have therapeutic significance for neuropsychiatric diseases related to stress.

关键词： amygdala stress c-fos SK channel anxiogesis

Projection-specific adaptation of amygdala neurons underlies anxiogesis by chronic stress in mice

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Projection-specific adaptation of amygdala neurons underlies...

中国神经科学学会第十二届全国学术会议

作者： Wen-Hua Zhang Wei-Zhu Liu Wen-Jie You Jun-Yu Zhang Zhi-Peng Liu bing-xing pan Laboratory of Fear and Anxiety Disorders Institute of Life Science Nanchang University

Persistent activation of amygdala underlies adversity of prolonged stress on emotion. However, little is known about the engagement of individual amygdala neurons, which are topographically intermingled but dispersed into distinct functional circuits. Here, we report that adaptation of mice basal-amygdala projection neurons（BA PNs） to chronic but not acute stress varies with their projection targets. While the BA PNs, regardless of whether they project to medial prefrontal cortex（mPFC）, quickly habituate to acute stress, those with efferent terminals bypassing（BY-mPFC PNs） but not targeting mPFC（TA-mPFC PNs） become persistently activated upon prolonged stress. Such projection-specific adaptation is caused by preferential reduction of SK channel currents in BY-m PFC PNs. Importantly, the SK current in BY-m PFC PNs but not their TA-mPFC counterparts is essential for anxiogesis subsequent to chronic stress. Our findings thus establish maladaptation of one subset of amygdala neurons as a pivotal mechanism for stress-related neuropsychopathologies.

关键词： Chronic stress anxiogesis amygdala projection-specific adaptation

GABA_(A)(δ)receptor hypofunction in the amygdala-hippocampal circuit underlies stress-induced anxiety

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Science Bulletin 2022年第1期67卷 97-110,M0004页

作者： Xia Qin Han-Qing pan Shou-He Huang Jia-Xin Zou Zhi-Heng Zheng Xiao-Xuan Liu Wen-Jie You Zhi-Peng Liu Jun-Li Cao Wen-Hua Zhang bing-xing pan Laboratory of Fear and Anxiety Disorders Institute of Life ScienceNanchang UniversityNanchang 330031China Department of Biological Science School of Life ScienceNanchang UniversityNanchang 330031China Department of Ophthalmology The Second Affiliated HospitalMedical School of Nanchang UniversityNanchang 330031China Jiangsu Provincial Key Laboratory of Anesthesiology Xuzhou Medical UniversityXuzhou 221004China

Dysregulated GABAergic inhibition in the amygdala has long been implicated in stress-related neuropsychiatric ***,the molecular and circuit mechanisms underlying the dysregulation remain ***,by using a mouse model of chronic social defeat stress(CSDS),we observed that the dysregulation varied drastically across individual projection neurons(PNs)in the basolateral amygdala(BLA),one of the kernel amygdala subregions critical for stress *** persistently reducing the extrasynaptic GABAAreceptor(GABA_(A)R)-mediated tonic current in the BLA PNs projecting to the ventral hippocampus(BLA→v HPC PNs),CSDS increased the current in those projecting to the anterodorsal bed nucleus of stria terminalis(BLA→adBNST PNs),suggesting projection-based dysregulation of tonic inhibition in BLA PNs by *** and electrophysiological analysis revealed that the opposite CSDS influences were mediated by loss-and gain-of-function ofδ-containing GABA_(A)Rs(GABA_(A)(δ)Rs)in BLA→vHPC and BLA→adBNST PNs,***,it was the lost inhibition in the former population but not the augmentation in the latter population that correlated with the increased anxiety-like behavior in CSDS *** mediated maintenance of GABA_(A)(δ)R currents in BLA→vHPC PNs occluded CSDS-induced anxiety-like *** findings clarify the molecular substrate for the dysregulated GABAergic inhibition in amygdala circuits for stress-associated psychopathology.

关键词： Chronic stress Anxiety Amygdala circuit Tonic inhibition GABAA(δ)R

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Enhancement of cortical inputs to lateral amygdala and suppression of fear in mice with restricted knockout of Rap 1

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Enhancement of cortical inputs to lateral amygdala and suppr...

中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： bing-xing pan,Shu-Jun WANG,Li-Ping ZHENG,Min WANG,Xin ZHANG Institute of Life Science,Nanchang University,Nanchang 330031,China

＜正＞Auditory fear conditioning is likely mediated by plastic changes in two inputs entering the lateral amygdala （LA）,one from the auditory thalamus and the other from auditory *** inputs enter LA via internal and external capsule ***,the specific roles of these inputs are still *** have been made using anatomic lesions to disclose their roles in fear conditioning,which,unexpectedly,leads to contradictory *** an alternative and novel strategy to anatomic lesions,we here employed conditional mutation of Rap1,a small GTPase,which has been recently shown to be involved in AMPA receptor trafficking and long-term potentiation（LTP） of synaptic transmission in hippocampus as well as spatial learning by genetically ablating rap 1a/1b genes in mice using a Cre-recombinase under the control of CaMKIIα*** found that conditional inactivation of rap1 genes selectively altered synaptic transmission in the cortical but not thalamic inputs by increasing the number of quanta released by a single presynaptic action potential by about three folds,raising presynaptic glutamate release probability and disrupting presynaptically expressed long-term potentiation（LTP）.These alterations were accompanied by impaired fear learning and reduced anxiety-like behaviors,suggesting that modulation of synaptic transmission from cortex to LA only is sufficient to affect innate and learned fear.

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Stiffness-tunable biomaterials provide a good extracellular matrix environment for axon growth and regeneration

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Neural Regeneration Research 2025年第5期20卷 1364-1376页

作者： Ronglin Han Lanxin Luo Caiyan Wei Yaru Qiao Jiming Xie Xianchao pan Juan xing Department of Pathophysiology School of Basic Medical SciencesSouthwest Medical UniversityLuzhouSichuan ProvinceChina Department of Medicinal Chemistry School of PharmacySouthwest Medical UniversityLuzhouSichuan ProvinceChina

Neuronal growth, extension, branching, and formation of neural networks are markedly influenced by the extracellular matrix—a complex network composed of proteins and carbohydrates secreted by cells. In addition to providing physical support for cells, the extracellular matrix also conveys critical mechanical stiffness cues. During the development of the nervous system, extracellular matrix stiffness plays a central role in guiding neuronal growth, particularly in the context of axonal extension, which is crucial for the formation of neural networks. In neural tissue engineering, manipulation of biomaterial stiffness is a promising strategy to provide a permissive environment for the repair and regeneration of injured nervous tissue. Recent research has fine-tuned synthetic biomaterials to fabricate scaffolds that closely replicate the stiffness profiles observed in the nervous system. In this review, we highlight the molecular mechanisms by which extracellular matrix stiffness regulates axonal growth and regeneration. We highlight the progress made in the development of stiffness-tunable biomaterials to emulate in vivo extracellular matrix environments, with an emphasis on their application in neural repair and regeneration, along with a discussion of the current limitations and future prospects. The exploration and optimization of the stiffness-tunable biomaterials has the potential to markedly advance the development of neural tissue engineering.

关键词： alginate axon growth biomaterials extracellular matrix neural repair neurons neuroregeneration polyacrylamide polydimethylsiloxane stiffness

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Engineering atomic Rb-N configurations to tune radical pathways for highly selective photocatalytic H2O2 synthesis coupled with biomass valorization

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Journal of Energy Chemistry 2025年第1期100卷 215-225页

作者： Jiaye Li Shuang pan Yihuang Chen Qiong Liu College of Chemistry and Materials Engineering Wenzhou University Guangdong Provincial Key Laboratory of Chemical Measurement and Emergency Test Technology (China) Institute of Analysis Guangdong Academy of Sciences (China National Analytical CenterGuangzhou)

Photocatalytic oxygen reduction for hydrogen peroxide （H2O2） synthesis presents a green and costeffective production ***,achieving highly selective H2O2synthesis remains challenging,necessitating precise control over free radical reaction pathways and minimizing undesirable oxidative ***,we report for the visible light-driven simultaneous co-photocatalytic reduction of O2to H2O2and oxidation of biomass using the atomic rubidium-nitride modified carbon nitride（CNRb）.The optimized CNRb catalyst demonstrates a record photoreduction rate of 8.01 mM h-1for H2O2generation and photooxidation rate of 3.75 mM h-1for furfuryl alcohol to furoic acid,achieving a remarkable solar-to-chemical conversion （SCC） efficiency of up to 2.27%.Experimental characterizations and DFT calculation disclosed that the introducing atomic Rb–N configurations allows for the high-selective generation of superoxide radicals while suppressing hydroxyl free radical *** is because the Rb–N serves as the new alternative site to perceive a stronger connection position for O2adsorption and reinforce the capability to extract protons,thereby triggering a high selective redox product *** study holds great potential in precisely regulating reactive radical processes at the atomic level,thereby paving the way for efficient synthesis of H2O2coupled with biomass valorization.

关键词： Atomic economy Radical pathway regulation Rubidium atom coordination Biomass valorization