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Increased excitatory amino acid transporter 2 levels in basolateral amygdala astrocytes mediate chronic stress–induced anxiety-like behavior

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Neural Regeneration Research 2025年第6期20卷 1721-1734页

作者： Xirong Xu Shoumin Xuan Shuai Chen Dan Liu Qian Xiao Jie Tu Shenzhen Key Laboratory of Neuroimmunomodulation for Neurological Diseases Shenzhen-Hong Kong Institute of Brain ScienceShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina CAS Key Laboratory of Brain Connectome and Manipulation Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Brain Connectome and Behavior the Brain Cognition and Brain Disease Institute(BCBDI)Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina University of Chinese of Academy of Sciences BeijingChina Faculty of Life and Health Sciences Shenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhenGuangdong ProvinceChina

The conventional perception of astrocytes as mere supportive cells within the brain has recently been called into question by empirical evidence, which has revealed their active involvement in regulating brain function and encoding behaviors associated with ***, astrocytes in the basolateral amygdala have been found to play a role in the modulation of anxiety-like behaviors triggered by chronic stress. Nevertheless, the precise molecular mechanisms by which basolateral amygdala astrocytes regulate chronic stress–induced anxiety-like behaviors remain to be fully elucidated. In this study, we found that in a mouse model of anxiety triggered by unpredictable chronic mild stress, the expression of excitatory amino acid transporter 2 was upregulated in the basolateral amygdala. Interestingly, our findings indicate that the targeted knockdown of excitatory amino acid transporter 2 specifically within the basolateral amygdala astrocytes was able to rescue the anxiety-like behavior in mice subjected to stress. Furthermore, we found that the overexpression of excitatory amino acid transporter 2 in the basolateral amygdala, whether achieved through intracranial administration of excitatory amino acid transporter 2agonists or through injection of excitatory amino acid transporter 2-overexpressing viruses with GfaABC1D promoters, evoked anxiety-like behavior in mice. Our single-nucleus RNA sequencing analysis further confirmed that chronic stress induced an upregulation of excitatory amino acid transporter 2 specifically in astrocytes in the basolateral amygdala. Moreover, through in vivo calcium signal recordings, we found that the frequency of calcium activity in the basolateral amygdala of mice subjected to chronic stress was higher compared with normal *** knocking down the expression of excitatory amino acid transporter 2 in the basolateral amygdala, the frequency of calcium activity was not significantly increased, and anxiety-like behavior was ob

关键词： anxiety astrocytes basolateral amygdala behavior dihydrokainic acid excitatory amino acid transporter 2 fiber photometry glutamate LDN-212320 transporter

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Glutamatergic CYLD deletion leads to aberrant excitatory activity in the basolateral amygdala:association with enhanced cued fear expression

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Neural Regeneration Research 2025年第11期20卷 3259-3272页

作者： Huidong Li Faqin Li Zhaoyi Chen Erwen Wu Xiaoxi Dai Danni Li Haojie An Shiyi Zeng Chunyan Wang Li Yang Cheng Long School of Life Sciences South China Normal UniversityGuangzhouGuangdong ProvinceChina School of Life Sciences Guangzhou UniversityGuangzhouGuangdong ProvinceChina Guangdong Provincial Key Laboratory of Major Obstetric Diseases The Third Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdong ProvinceChina South China Normal University-Panyu Central Hospital Joint Laboratory of Translational Medical Research Panyu Central HospitalGuangzhouGuangdong ProvinceChina

Neuronal activity,synaptic transmission,and molecular changes in the basolateral amygdala play critical roles in fear ***(CYLD)is a deubiquitinase that negatively regulates the nuclear factor kappa-B *** is well studied in non-neuronal cells,yet underinvestigated in the brain,where it is highly *** studies have shown involvement of CYLD in the remodeling of glutamatergic synapses,neuroinflammation,fear memory,and anxiety-and autism-like ***,the precise role of CYLD in glutamatergic neurons is largely ***,we first proposed involvement of CYLD in cued fear *** next constructed transgenic model mice with specific deletion of Cyld from glutamatergic *** results show that glutamatergic CYLD deficiency exaggerated the expression of cued fear in only male ***,loss of CYLD in glutamatergic neurons resulted in enhanced neuronal activation,impaired excitatory synaptic transmission,and altered levels of glutamate receptors accompanied by over-activation of microglia in the basolateral amygdala of male ***,our study suggests a critical role of glutamatergic CYLD in maintaining normal neuronal,synaptic,and microglial *** may contribute,at least in part,to cued fear expression.

关键词： basolateral amygdala cued fear expression cylindromatosis deubiquitinase glutamate receptor 1 glutamatergic neuron microglial activation N-methyl-D-aspartate receptor 1 neuronal activation synaptic transmission

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Dip2a regulates stress susceptibility in the basolateral amygdala

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Neural Regeneration Research 2025年第6期20卷 1735-1748页

作者： Jing Li Zixuan He Weitai Chai Meng Tian Huali Yu Xiaoxiao He Xiaojuan Zhu Key Laboratory of Molecular Epigenetics Ministry of Education Institute of Genetics and CytologyNortheast Normal UniversityChangchunJilin ProvinceChina

Dysregulation of neurotransmitter metabolism in the central nervous system contributes to mood disorders such as depression, anxiety, and post–traumatic stress disorder. Monoamines and amino acids are important types of neurotransmitters. Our previous results have shown that disco-interacting protein 2 homolog A(Dip2a) knockout mice exhibit brain development disorders and abnormal amino acid metabolism in serum. This suggests that DIP2A is involved in the metabolism of amino acid–associated neurotransmitters. Therefore, we performed targeted neurotransmitter metabolomics analysis and found that Dip2a deficiency caused abnormal metabolism of tryptophan and thyroxine in the basolateral amygdala and medial prefrontal cortex. In addition, acute restraint stress induced a decrease in 5-hydroxytryptamine in the basolateral amygdala. Additionally, Dip2a was abundantly expressed in excitatory neurons of the basolateral amygdala, and deletion of Dip2a in these neurons resulted in hopelessness-like behavior in the tail suspension test. Altogether, these findings demonstrate that DIP2A in the basolateral amygdala may be involved in the regulation of stress susceptibility. This provides critical evidence implicating a role of DIP2A in affective disorders.

关键词： 5-hydroxytryptamine acute restraint stress basolateral amygdala CaMKII neurons DIP2A metabolomics neurotransmitters principal component analysis stress susceptibility tryptophan

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Involvement of basolateral amygdala GABAA receptors in the effect of dexamethasone on memory in rats

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2011年第11期12卷 900-908页

作者： Lotfollah KHAJEHPOUR Acieh ALIZADEH-MAKVANDI Mahnaz KESMATI Hooman ESHAGH-HAROONI Department of Biology College of ScienceShahid Chamran University of Ahvaz

In this study we investigated whether GABAA receptors of the basolateral amygdala(BLA) interact with the effect of dexamethasone on the retrieval stage of *** male Wistar rats were bilaterally cannulated in the BLA by stereotaxic *** animals were trained in step-through apparatus by induction of electric shock(1.5 mA,3 s) and were tested for memory retrieval after 1 *** time of latency for entering the dark compartment of the instrument and the time spent by rats in this chamber were recorded for evaluation of the animals' retrieval in passive avoidance *** of dexamethasone(0.3 and 0.9 mg/kg,subcutaneously(s.c.)),immediately after training,enhanced memory *** effect was reduced by intra-BLA microinjection of muscimol(0.125,0.250 and 0.500 μg/rat),when administered before 0.9 mg/kg of *** of bicuculline(0.75 μg/rat,intra-BLA) with an ineffective dose of dexamethasone(0.1 mg/kg,s.c.) increased memory ***,the same doses of muscimol and bicuculline without dexamethasone did not affect memory *** data support reports that dexamethasone enhances memory *** seems that GABAA receptors of the BLA mediate the effect of dexamethasone on memory retrieval in rats.

关键词： basolateral amygdala Dexamethasone Muscimol Bicuculline Passive avoidance task

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Effects of D-serine on the basolateral amygdala and ventral tegmental area in model rats with conditioned fear memory

Effects of D-serine on the basolateral amygdala and ventral ...

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中国神经科学学会第十届全国学术会议

作者： Ling-Lu SUN Ming-Xun ZHANG Jun HUANG Meng-Ya WANG Cell Electrophysiology Laboratory Wannan Medical College Rising-Star Group Wannan Medical College

Objective To explore the possible mechanisms underlying D-serine therapy of post-traumatic stress disorder（PTSD） by observing its effects on the basolateral amygdala（BLA） and ventral tegmental area（VTA） in model rats with conditioned fear *** A protocol of 3-day "sound- electric shock" paired stimulation was used to prepare rat model of conditioned fear memory indicated by an increase of percentage of freezing *** the extracellular recordings from BLA and VTA in the brain were conducted,and physiological functions including electrocardiograph,electromyography,skin conductance and body temperature were simultaneously monitored from the urethane-anesthetized normal and model rats（n=4）.Effects of D-serine（0.4 g/kg,i.p.） were observed as compared with saline（i.p.）.Results Although no significant differences of bioelectrical activities of BLA and VTA,and physiological functions were observed between normal and model rats,saline injection significantly increased firing rate only in BLA in normal rats,while in BLA and VTA in model ***,D-serine induced a significant increase of the firing rate of BLA and VTA in normal rats,but only of VTA in model ***,the increase of firing rate of VTA by D-serine was higher in model rats than in normal rats（P＜0.05）.Conclusion These preliminary results suggest D-serine may have more potent activating effects on VTA than BLA in model rats,and on VTA in model rats than in normal rats.

关键词： D-serine basolateral amygdala ventral tegmental area post-traumatic stress disorder

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Pre-synaptic TrκB in basolateral amygdala neurons mediates BDNF signaling transmission in memory extinction

Pre-synaptic TrκB in basolateral amygdala neurons mediates ...

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第十二届全国免疫学学术大会

作者： Li Yuan shandong University Basic Medical School

Brain-derived neurotrophic factor(BDNF)and its high affinity receptor,TrkB,play an essential role in memory *** previous work has shown that JIP3(JNK interacted protein 3)mediates anterograde axonal transport of TrkB ... 详细信息

关键词： CCl-EGFP pre-synaptic TrkB basolateral amygdala memory extinction

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Gnas methylation in the basolateral amygdala regulates reconsolidation of morphine associated memory in rats

Gnas methylation in the basolateral amygdala regulates recon...

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第六届心理健康学术年会

作者： Jianjun Zhang Peng Liu Fengze Jiang Nan Sui CAS Key Laboratory of Mental Health Institute of Psychology Department of Psychology University of Chinese Academy of Sciences

Recently, we and other laboratories reported that DNA methyltransferases(Dnmts)were involved in the reconsolidation of addiction related memory, but how DNA methylation regulates reconsolidation of opiate reward memory remain to be found. Here, using morphine induced conditioned place preference(mCPP) in rats, we showed that Dnmts inhibition in basolateral amygdala(BLA), but not in central amygdala or nucleus accumbens, disrupted reconsolidation of morphine reward memory. Moreover, the disruption effects were retrieval-and time-window-dependent. Concordant with this, the mRNA levels of Dnmt 3 a and Dnmt 3 b but not Dnmt 1 in the BLA were significantly upregulated since one hour after memory retrieval. Thus, we further explored the target genes of DNA methylation in the BLA at one hour after retrieval and found 75 differentially methylated regions. Then, we verified the DNA methylation and the roles of three genes(Pik3 r1, Gnas and Sox10) whose promoter were hypermethylated in *** DNA methylation level of these genes were upregulated and the mRNA levels were downregulated. Intra-BLA injection of the PI3 K agonist 740 Y-P immediately after memory retrieval impaired the reconsolidation, and BLA-specific overexpression of Gnas significantly disrupted the reconsolidation. However, overexpression of Sox10 in BLA did not affect this process. These data demonstrated that DNA methylation in BLA, mediated by Dnmt 3 a and/or Dnmt 3 b, regulated reconsolidation of morphine reward memory via hypermethylation of Gnas promotor.

关键词： DNA methylation reconsolidation morphine basolateral amygdala Dnmts Gnas

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TRPV1 in basolateral amygdala mediates visceral hypersensitivity in adult rats with neonatal maternal deprivation

TRPV1 in basolateral amygdala mediates visceral hypersensiti...

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中国生理学会消化与营养专业委员会成立大会暨第一届学术会议

作者： Ying Xiao Ping-An Zhang Qiya Xu Hang Zheng Youlang Zhou 徐广银 Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases Laboratory of Translational Pain Medicine Institute of Neuroscience Soochow University 苏州大学神经科学研究所

Chronic stress exacerbates or causes relapse of symptoms such as abdominal pain and cramping in patients with irritable bowel syndrome(IBS).Neonatal maternal deprivation(NMD)as an animal model used to study the mechanism of IBS may cause visceral hypersensitivity in adult rats.A growing body of evidence demonstrates that central amygdala(CeA)plays an important role in the modulation of visceral *** as one of the input pathways to CeA the role of basolateral amygdala(BLA)in the modulation of pain remains *** arc highest densities of TRPV1 labeled neurons within BLA and TRPV1 was found to take part in peripheral pain *** study is to determine whether TRPV1 in BLA mediates visceral hypersensitivity induced in adult rats with neonatal maternal *** hypersensitivity was induced by neonatal maternal deprivation(NMD)and was quantified by abdominal withdrawal *** of TRPV1 was determined by Western *** synaptic transmission of neurons in BLA was recorded by patch *** was found that the expression of TRPV1 in BLA was significantly upregulated in NMD rats;glutamatergic synaptic activities in BLA were increased in NMD rats;application of capsazepine(TRPV1 antagonist)decreased glutamatergic synaptic activities of BLA neurons in NMD slices through a presynaptic mechanism;application of capsaicin(TRPV1 agonist)increased glutamatergic synaptic activities of BLA neurons in control slices through presynaptic mechanism without affecting GABAergic synaptic activities;microinjecting capsazepine into BLA significantly increased colonic distension threshold both in control and NMD *** data suggested that upregulation of TRPV1 in BLA contributes to visceral hypersensitivity of NMD rats through enhancing excitaion of BLA thus identifying a potential target for treatment of chronic visceral pain.

关键词： Neonatal maternal deprivation Visceral hypersensitivity TRPV1 basolateral amygdala Presynaptic mechanism

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amygdala neural ensemble mediates mouse social investigation behaviors

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National Science Review 2023年第1期10卷 108-126页

作者： Ji-an Wei Qing Han Zhihua Luo Linglin Liu Jing Cui Jiahui Tan Billy K.C.Chow Kwok-Fai So Li Zhang Key Laboratory of CNS Regeneration(Ministry of Education) Guangdong-Hong Kong-Macau Institute of CNS RegenerationJinan University School of Biological Sciences The University of Hong Kong State Key Laboratory of Brain and Cognitive Science Li Ka Shing Faculty of Medicine The University of Hong Kong Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay Area Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) Co-Innovation Center of Neuroregeneration Nantong University Neuroscience and Neurorehabilitation Institute University of Health and Rehabilitation Sciences Institute of Clinical Research for Mental Health Jinan University

Innate social investigation behaviors are critical for animal survival and are regulated by both neural circuits and neuroendocrine *** understanding of how neuropeptides regulate social interest,however,is incomplete at the current *** this study,we identified the expression of secretin(SCT) in a subpopulation of excitatory neurons in the basolateral *** distinct mole cular and physiological features,BLASCT+cells projected to the medial prefrontal cortex and were necessary and sufficient for promoting social investigation behaviors,whilst other basolateral amygdala neurons were anxiogenic and antagonized social ***,the exogenous application of secretin effectively promoted social interest in both healthy and autism spectrum disorder model *** results collectively demonstrate a previously unrecognized group of amygdala neurons for mediating social behaviors and suggest promising strategies for social deficits.

关键词： social interaction basolateral amygdala secretin

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Whole-Brain Map of Long-Range Monosynaptic Inputs to Different Cell Types in the amygdala of the Mouse

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Neuroscience Bulletin 2020年第11期36卷 1381-1394页

作者： Jia-Yu Fu Xiao-Dan Yu Yi Zhu Shi-Ze Xie Meng-Yu Tang Bin Yu Xiao-Ming Li Center for Neuroscience and Department of Neurology of Second Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China NHC and CAMS Key Laboratory of Medical Neurobiology Center for Brain Science and Brain-Inspired IntelligenceGuangdong-Hong Kong-Macao Greater Bay AreaJoint Institute for Genetics and Genome Medicine between Zhejiang University and University of TorontoHangzhou 310058China

The amygdala,which is involved in various behaviors and emotions,is reported to connect with the whole ***,the long-range inputs of distinct cell types have not yet been ***,we used a retrograde trans-synaptic rabies virus to generate a whole-brain map of inputs to the main cell types in the mouse *** identified 37 individual regions that projected to neurons expressing vesicular glutamate transporter 2,78 regions to parvalbumin-expressing neurons,104 regions to neurons expressing protein kinase C-δ,and 89 regions to somatostatin-expressing *** amygdala received massive projections from the isocortex and *** nuclei,such as the caudate-putamen and the CA1 field of the hippocampus,exhibited input preferences to different cell types in the ***,we identified several novel input areas,including the substantia innominata and zona *** findings provide anatomical evidence to help understand the precise connections and diverse functions of the amygdala.

关键词： basolateral amygdala Central amygdala Rabies virus retrograde tracing Glutamatergic GABAergic Mouse

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