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Inhibitory gamma-aminobutyric acidergic neurons in the anterior cingulate cortex participate in the comorbidity of pain and emotion

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Neural Regeneration Research 2025年第10期20卷 2838-2854页

作者： Lu Guan Mengting Qiu Na Li Zhengxiang Zhou Ru Ye Liyan Zhong Yashuang Xu Junhui Ren Yi Liang Xiaomei Shao Jianqiao Fang Junfan Fang Junying Du Department of Neurobiology and Acupuncture Research Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Key Laboratory for Research of Acupuncture Treatment and Transformation of Emotional Diseases Third School of Clinical MedicineZhejiang Chinese Medical UniversityHangzhouZhejiang ProvinceChina Fuchun Community Health Service Center of Fuyang District HangzhouZhejiang ProvinceChina

Pain is often comorbid with emotional disorders such as anxiety and *** of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid *** review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain *** understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these ***,the mechanisms that regulate gamma-aminobutyric acidergic systems remain *** is also unclear as to whether the mechanisms are presynaptic or *** exploration of the complexities of this system may reveal new pathways for research and drug development.

关键词： anterior cingulate cortex anxiety chronic pain circuit communication comorbidity depression gamma-aminobutyric acidergic neurons parvalbumin neurons synaptic transmission

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anterior cingulate cortex Mediates Hyperalgesia and Anxiety Induced by Chronic Pancreatitis in Rats

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Neuroscience Bulletin 2022年第4期38卷 342-358页

作者： Dan Ren Jia-Ni Li Xin-Tong Qiu Fa-Ping Wan Zhen-Yu Wu Bo-Yuan Fan Ming-Ming Zhang Tao Chen Hui Li Yang Bai Yun-Qing Li Department of Anatomy Guangxi Medical UniversityNanning 510000China Department of Anatomy Histology and Embryology and K.K.Leung Brain Research CentreFourth Military Medical UniversityXi’an 710032China Department of Anatomy Xuzhou Medical UniversityXuzhou 221004China Department of Cardiology The Second Affiliated Hospital of Xian Jiaotong UniversityXi’an 710004China Department of Neurosurgery General Hospital of Northern Theater CommandShenyang 110016China Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province Haikou 570216China Department of Human Anatomy College of Basic MedicineDali UniversityDali 671000China

Central sensitization is essential in maintaining chronic pain induced by chronic pancreatitis(CP),but cortical modulation of painful CP remains ***,we examined the role of the anterior cingulate cortex(ACC)in the pathogenesis of abdominal hyperalgesia in a rat model of CP induced by intraductal administration of trinitrobenzene sulfonic acid(TNBS).TNBS treatment resulted in long-term abdominal hyperalgesia and anxiety in *** data indicated that painful CP induced a significant increase in FOS-expressing neurons in the nucleus tractus solitarii(NTS)and ACC,and some FOS-expressing neurons in the NTS projected to the *** addition,a larger portion of ascending fibers from the NTS innervated pyramidal neurons,the neural subpopulation primarily expressing FOS under the condition of painful CP,rather than GABAergic neurons within the *** rats showed increased expression of vesicular glutamate transporter 1,and increased membrane trafficking and phosphorylation of the N-methyl-D-aspartate receptor(NMDAR)subunit NR2B and theα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor(AMPAR)subunit GluR1 within the *** of NMDAR and AMPAR antagonists into the ACC to block excitatory synaptic transmission significantly attenuated abdominal hyperalgesia in CP rats,which was similar to the analgesic effect of endomorphins injected into the *** inhibiting the excitability of ACC pyramidal cells via chemogenetics reduced both hyperalgesia and comorbid anxiety,whereas activating these neurons via optogenetics failed to aggravate hyperalgesia and anxiety in CP *** together,these findings provide neurocircuit,biochemical,and behavioral evidence for involvement of the ACC in hyperalgesia and anxiety in CP rats,as well as novel insights into the cortical modulation of painful CP,and highlights the ACC as a potential target for neuromodulatory interventions in the treatment of painful CP.

关键词： Chronic pancreatitis anterior cingulate cortex Nucleus tractus solitaries Hyperalgesia Anxiety

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Role of the anterior cingulate cortex in Translational Pain Research

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Neuroscience Bulletin 2021年第3期37卷 405-422页

作者： Xiao Xiao Ming Ding Yu-Qiu Zhang Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence Ministry of EducationInstitute of Science and Technology for Brain-Inspired IntelligenceBehavioral and Cognitive Neuroscience CenterFudan UniversityShanghai 200433China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Department of Translational NeuroscienceJing’an District Centre Hospital of ShanghaiInstitutes of Brain ScienceInstitute of Integrative MedicineFudan UniversityShanghai 200032China

As the most common symptomatic reason to seek medical consultation,pain is a complex experience that has been classified into different categories and *** pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well *** this review,we elaborate the commonalities and differences from accumulated evidence by a variety of pain assays for physiological pain and pathological pain including inflammatory pain,neuropathic pain,and cancer pain in the ACC,and discuss the cellular receptors and signaling molecules from animal *** further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain *** comprehensive understanding of pain processing in the ACC may lead to bridging the gap in translational research between basic and clinical studies and to develop new therapies.

关键词： anterior cingulate cortex Deep brain stimulation Transcranial magnetic stimulation Transcranial direct current stimulation Pathological pain Inflammatory pain Neuropathic pain Cancer pain

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Spatial and temporal plasticity of synaptic organization in anterior cingulate cortex following peripheral inflammatory pain: multi-electrode array recordings in rats

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Neuroscience Bulletin 2014年第1期30卷 1-20页

作者： Yun-Fei Lu Yan Wang Ying He Fu-Kang Zhang Ting He Rui-Rui Wang Xue-Feng Chen Fei Yang Ke-Rui Gong Jun Chen Institute for Biomedical Sciences of Pain and Institute for Functional Brain Disorders Tangdu Hospital The Fourth Military Medical University Key Laboratory of Brain Stress and Behavior PLA Institute for Biomedical Sciences of Pain Capital Medical University

To explore whether experiencing inflammatory pain has an impact upon intracortical synaptic organization, the planar multi-electrode array （MEA） technique and 2-dimensional current source density （2D-CSD） imaging were used in slice preparations of the anterior cingulate cortex （ACC） from rats. Synaptic activity across different layers of the ACC was evoked by deep layer stimulation through one electrode. The layer-localization of both local field potentials （LFPs） and the spread of current sink calculated by 2D-CSD analysis was characterized pharmacologically. Moreover, the induction of long-term potentiation （LTP） and changes in LTP magnitude were also evaluated. We found that under naive conditions, the current sink was initially generated in layer Ⅵ, then spread to layer Ⅴ and finally confined to layers Ⅱ-Ⅲ. This spatial pattern of current sink movement typically reflected changes in depolarized sites from deep layers （Ⅴ-Ⅵ） to superficial layers （Ⅱ-Ⅲ） where intra- and extra- cortical inputs terminate. In the ACC slices from rats in an inflamed state （for 2 h） caused by intraplantar bee-venom injection, the spatial profile of intra-ACC synaptic organization was significantly changed,showing an enlarged current sink distribution and a leftward shift of the stimulus-response curves relative to the naive and saline controls. The change was more distinct in the superficial layers （Ⅱ-Ⅲ） than in the deep site. In terms of temporal properties, the rate of LTP induction was significantly increased in layers Ⅱ-Ⅲ by inflammatory pain. However, the magnitude of LTP was not significantly enhanced by this treatment. Taken together, these results show that inflammatory pain results in distinct spatial and temporal plasticity of synaptic organization in the ACC, which may lead to altered synaptic transmission and modulation.

关键词： anterior cingulate cortex multi-electrodearray synaptic plasticity intracortical synapticorganization pain

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Activation of extracellular signal-regulated kinase in the anterior cingulate cortex contributes to the induction of long-term potentiation in rats

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Neuroscience Bulletin 2009年第5期25卷 301-308页

作者：曹红崔一卉赵志奇曹晓华张玉秋复旦大学脑科学研究院医学神经生物学国家重点实验室神经生物研究所上海200032 华东师范大学脑功能基因组学教育部重点实验室上海市科学技术委员会重点实验室上海200062

Objective To explore the role of the extracellular signal-regulated kinase （ERK）/cAMP response element binding protein （CREB） pathway in the induction of long-term potentiation （LTP） in the anterior cingulate cortex （ACC） that may be implicated in pain-related negative emotion. Methods LTP of field potential was recorded in ACC slice and the expressions of phospho-ERK （pERK） and phospho-CREB （pCREB） were examined using immunohistochemistry method. Results LTP could be induced stably in ACC slice by high frequency stimulation （2-train, 100 Hz, 1 s）, while APv （an antagonist of NMDA receptor） could block the induction of LTP in the ACC, indicating that LTP in this experiment was NMDA receptor-dependent. Bath application of PD98059 （50 μmol/L）, a selective MEK inhibitor, at 30 min before tetanic stimulation could completely block the induction of LTP. Moreover, the protein level of pERK in the ACC was transiently increased after LTP induction, starting at 5 rain and returning to basal at 1 h after tetanic stimulation. The protein level of pCREB was also increased after LTP induction. The up-regulation in pERK and pCREB expressions could be blocked by pretreatment of PD98059. Double immunostaining showed that after LTP induction, most pERK was co-localized with pCREB. Conclusion NMDA receptor and ERK-CREB pathway are necessary for the induction of LTP in rat ACC and may play important roles in pain emotion.

关键词： long-term potentiation extracellular signal-regulated kinase cAMP response element binding protein anterior cingulate cortex rat

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Differential effects of long and short train theta burst stimulation on LTP induction in rat anterior cingulate cortex slices:Multi-electrode array recordings

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Neuroscience Bulletin 2009年第5期25卷 309-318页

作者：何莹刘明刚巩克瑞陈军首都医科大学疼痛生物医学研究所北京100069 第四军医大学附属唐都医院疼痛生物医学研究所西安710038

Objective There is substantial evidence supporting the notion that the anterior cingulate cortex （ACC） is an important limbic structure involved in multiple brain functions such as sensory perception, motor conflict monitoring, memory, emotion and cognition. It has been shown that long term potentiation （LTP） is an important synaptic model of neural plasticity in the ACC, however, little is known about the spatiotemporal properties of ACC at network level. The present study was designed to see the LTP induction effects across different layers of the ACC by using different conditioning stimuli （CS） protocols. Methods A unique multi-electrode array recording technique was used in the acutely-dissociated ACC slices of rats. Long and short train theta burst stimulation （TBS） paradigms were applied in layer V-VI as the CS and the LTP induction effects were compared across different layers of the ACC. Briefly, both long and short train TBS are composed of bursts （4 pulses at 100 Hz） with a 200 ms interval, however, the former （TBS1） was with 10 trains and the latter （TBS2） was with 5 trains. After test stimulation at layer V-VI in the ACC, network field potentials （FPs） could be simultaneously recorded across all layers of the ACC. Results The waveforms of FPs were different across different layers. Namely, positive-going waveforms were recorded in layer I and negative-going waveforms were recorded in layers V-VI, in contrast, complex waveforms were localized mainly in layers II-III. Following application of two CS protocols, the induction rate of LTP was significantly different between TBS 1 and TBS2 regardless of the spatial properties. TBS1 had more than 60% success, while TBS2 was less than 25% in induction of LTP. Moreover, both the 2 CS protocols could induce LTP in layers II-III and layers V-VI without layer-related difference. However, no LTP was inducible in layer I. Conclusion The present findings indicate that stimulation protocols may, at least in part, accoun

关键词： long term potentiation anterior cingulate cortex theta burst stimulation multi-electrode array recordings rat

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Neuropsychological Profile of a Patient with Acquired Brain Damage Following Vascular Lesion of the Left anterior cingulate cortex

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Neuroscience & Medicine 2024年第1期15卷 66-75页

作者： Jimmy Zúñiga-Márquez Lina Borda-Camargo Diego Buitrago-Mora Lorely Guerra-Valdés Laura González Patricia Quintero-Cusgüen Nataly Gutierrez-Ávila Hospital Universitario de la Samaritana Bogotá Colombia Neuropsychological Assessment and Diagnosis Graduate Program School of Psychology Universidad San Buenaventura Bogotá Bogotá Colombia

Stroke is a physiological alteration associated with changes in blood flow that can result in sudden-onset cognitive impairment. It has a heterogenous clinical presentation with varying degrees of severity correlated with specific central nervous system zones or areas, and its prognosis is uncertain. This case study describes a 62-year-old male patient with acquired brain damage of the anterior cingulate cortex as a result of an ischemic event in the territory of the left anterior cerebral artery. Cognitive function was assessed using the neuropsychological executive function and frontal lobe test battery (BANFE-2) as well as other neuropsychological tests. The results show a profile of higher mental functions characterized by the presence of dysexecutive syndrome with marked behavioral alteration and diencephalic amnesia. .

关键词： Ischemic Stroke anterior cingulate cortex Neuropsychology Acquired Brain Damage

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Electroacupuncture Alleviates Anxiety-like Behavior in Pain Aversion Rats by Attenuating the Expression of Neuropeptide Y in anterior cingulate cortex

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Clinical Complementary Medicine and Pharmacology 2022年第2期2卷 10-18页

作者： Fangbing Shao Junying Du Sisi Wang Rok Cerne Junfan Fang Xiaomei Shao Xiaoming Jin Jianqiao Fang Department of Neurobiology and Acupuncture Research the Third School of Clinical MedicineZhejiang Chinese Medical University.Hangzhou 310053ZhejiangChina Indiana Spinal Cord and Brain Injury Research Group Stark Neuroscience Research Institute&Department of AnatomyCell Biology and PhysiologyIndiana University School of MedicineIndianapolis 46202IndianaUSA

Background:Pain is considered as a multidimensional conscious experience that includes a sensory component and a negative affective-motivational ***(EA)is widely used to treat pain and paininduced negative emotions,however,little is known about the mechanisms underlying the effect of ***:This study investigated the effect of EA on alleviating the anxiety-like behaviors in pain aversion rats and its anterior cingulate cortex(ACC)regulation ***:After a Freund’s complete adjuvant(CFA)-conditioned place aversion(C-CPA)model was established in rats,EA treatment(2/100 Hz,30 min,once/day,4 days totally)was applied at bilateral Zusanli(ST36)and Kunlun(BL60)*** Frey filaments were used to measure changes of pain withdrawal threshold(PWT)at indicated time *** zero maze(EZM)was used to investigate the changes of pain-related anxiety and CPA was used to investigate the changes of pain *** protein expression levels of GAD67,PV,and NPY in ACC were detected by Western ***:Compared with the control group,the staying time in the"CFA-paired compartment"was significantly reduced,and the PWT was decreased in model *** the EZM assessment,the distance and the time in open arm,as well as the number of open arm entries of model group were significantly lower than those in the control *** the CPA assessment,the time spent in the"CFA-paired compartment"was significantly decreased in model group compared with control group,and EA reversed the changes in pain sensation and in pain-related *** blotting showed that the NPY level,but not the levels of GAD67 and PV,was significantly increased in the ACC of the model group compared to that of the control *** increased expression of NPY in the ACC was significantly downregulated by EA,while sham EA produced no such ***:EA can effectively relieve the pain and pain-related emotions,and its mechanism may be achieved by

关键词： Electroacupuncture Chronic pain anterior cingulate cortex Aversion Anxiety Neuropeptide Y

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Functional Connection between anterior cingulate cortex and Orbital Frontal cortex in Risk-Based Decision Making in Rats

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神经药理学报 2019年第4期 39-40页

作者： WANG Yu-chen YANG Sha-sha XU Rui HUANG Wen-qiang HONG Dan-dan GAO Wen-jun ZHOU Ning YU Ping

Risk-based decision making is the selection of a behavior option when its potential value and the probability in redeeming its value are already known. Both anterior cingulate cortex( ACC) and orbital frontal cortex( OFC) participate in risk-based decision making. However,whether ACC and OFC play different roles and how they cooperate in this process remains unclear. In this study,by using probability-discounting task paradigm and multiple channel recordings,we simultaneously recorded the neuronal discharges and local filed potential in ACC and OFC when the rat was performing the risk-based decision-making task. We found that both ACC and OFC contained three types of neurons exhibiting specific discharging patterns,including prediction neurons,action + award neurons,and award neurons. Particularly,ACC and OFC prediction neurons exhibit different discharging patterns between risky and conservative choices and between the different probabilities of large/risky award. It means that they were both sensitive to the information about the probability of award. We also find rhythmic oscillation in the ACC and OFC exhibit specific coherent activities among the different probabilities of large/risky award at decision-making point. The tendency of low-risky blocks( 50% block and 100% block) increased sharply before pressing,while rose slowly in 50% block and keep the baseline level in 100% block. Moreover,the average coherence showed that the average coherence was no significant difference in low-probability blocks but showed significant difference in highprobability blocks. These findings provide the first evidence of different roles of ACC and OFC in risky decision making and reveals the functional connection between the two brain areas during isk-based decision making.

关键词： anterior cingulate cortex orbital frontal cortex decision making risk-based decision-making task in vivo recording rat

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Neonatal Ketamine Exposure Causes Impairment of Long-term Synaptic Plasticity in the anterior cingulate cortex of Rats

Neonatal Ketamine Exposure Causes Impairment of Long-term Sy...

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中国生理学会第24届全国会员代表大会暨生理学学术大会

作者：陈军王蕊蕊李震王燕吕云飞孙薇第四军医大学唐都医院疼痛生物医学研究所首都医科大学疼痛生物医学研究所美国德州大学阿灵顿分校心理系

Ketamine,a dissociative anesthetic most commonly used in many pediatric procedures,has been reported to cause widespread neuroapoptosis in the neonatal brain after exposure in high doses and/orfor prolonged *** neurodegenerative change occurs most severely in the forebrain including the anterior cingulated cortex(ACC)that is an important brain structure for mediating a variety of cognitive ***,it is still unknown whether this developmental neuroapoptosis affects the synaptic plasticity of the ACC in *** this study,we performed whole-cell patch-clamp recordings from the ACC of adult rat brain slices to examine any alterations in long-term synaptic plasticity caused by neonatal ketamine *** was administered at postnatal day 4-7(subcutaneous injections,20 mg/kg given six times,once every 2 h).At 3-4 weeks of age,long-term potentiation(LTP)was induced and recorded by monitoring excitatory postsynaptic currents from ACC *** found that the induction of LTP in the ACC was significantly reduced when compared to the control *** LTP impairment was accompanied by an increase intheα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated excitatory synaptic transmission and a decrease in GABA inhibitory synaptic transmission in the pyramidal neurons of the ***,our present findings show that neonatal ketamine exposure causes a significant LTP impairment in the *** suggest that the imbalanced synaptic transmission is likely to contribute to ketamine-induced LTP impairment in the ACC.

关键词： ketamine anterior cingulate cortex long-term potentiation excitatory synaptic transmission inhibitory synaptic transmission

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