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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

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 elusive.Here,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 rats.Morphological 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 ACC.In 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 ACC.CP 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 ACC.Microinjection 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 ACC.Specifically 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 rats.Taken 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

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

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 stages.In pain processing,noxious stimuli may activate the anterior cingulate cortex(ACC).But the function of ACC in the different pain conditions is not well discussed.In 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 studies.We further summarize the ACC as a new central neuromodulation target for invasive and non-invasive stimulation techniques in clinical pain management.The 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

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

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 component.Electroacupuncture(EA)is widely used to treat pain and paininduced negative emotions,however,little is known about the mechanisms underlying the effect of EA.Objective:This study investigated the effect of EA on alleviating the anxiety-like behaviors in pain aversion rats and its anterior cingulate cortex(ACC)regulation mechanism.Methods: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)acupoints.Von Frey filaments were used to measure changes of pain withdrawal threshold(PWT)at indicated time points.Elevated zero maze(EZM)was used to investigate the changes of pain-related anxiety and CPA was used to investigate the changes of pain aversion.The protein expression levels of GAD67,PV,and NPY in ACC were detected by Western blotting.Results:Compared with the control group,the staying time in the"CFA-paired compartment"was significantly reduced,and the PWT was decreased in model group.In 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 group.In 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 emotions.Western 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 group.The increased expression of NPY in the ACC was significantly downregulated by EA,while sham EA produced no such effect.Conclusion:EA can effectively relieve the pain and pain-related emotions,and its mechanism may be achieved by down-regulating the expression of NPY in the ACC

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

Rapid effect of estrogen on glutamate related synaptic transmission and plasticity in the anterior cingulate cortex

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Rapid effect of estrogen on glutamate related synaptic trans...

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： Xiao XIAO,Yan ZHANG,Zhi-Qi ZHAO,Yu-Qiu ZHANG~* Institute of Neurobiology,Institutes of Brain Science and State Key Laboratory of Medical Neurobiology,Fudan University,Shanghai 200032,China

＜正＞Classically,estrogen has multiple actions in the brain via genomic mechanisms which generally take several hours.The present study was designed to examine that whether estrogen regulates glutamatergic transmission and plasticity within minutes and what is the possible mechanisms underlying the estrogen-induced rapid effects in the anterior cingulate cortex（ACC）.Immunohistochemistry results revealed that estrogen receptors（ERs） were highly expressed in glutamatergic neurons of the ACC.Whole-cell recording from ACC slices results showed that estrogen enhanced the glutamatergic excitatory postsynaptic currents（EPSCs） in a dose-dependent fashion.However,the affect of estrogen on AMPA and NMDA transmission exhibited an opposite manifestation:NMDA-mediated EPSCs（NMDAEPSCs） were significantly enhanced;whereas AMPA-EPSCs were remarkably inhibited.The fast onset effect of enhanced NMDA-EPSCs,within 6 minutes bath application of estrogen,lasted for more than 30 minutes（NMDA- LTP）.This NMDA-LTP was blocked by ER antagonist（ICI 182780） and was mimicked by E-BSA,a specific agonist of membrane ER.Moreover,the induction of estrogen-induced NMDA-LTP was also prevented by NR2B inhibitor and PKA inhibitor.Taken together,these findings implicate that estrogen has rapid effects on glutamate transmission in ACC neurons.Also,estrogen-induced chemical NMDA-LTP is at least partially mediated by membrane ER.NR2BPKA pathway may play a critical role in estrogen-induced NMDA-LTP.

关键词： estrogen rapid effect NMDA receptor LTP anterior cingulate cortex

Activation of anterior cingulate cortex in rat subjected to double rotation eleciting motion sickness

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Activation of anterior cingulate cortex in rat subjected to ...

中国神经科学学会第四次会员代表大会暨第八届全国学术会议

作者： Fu-Xing ZHANG~*,Jin-Lian LI,Yun-Qing LI Department of Anatomy,Histology and embryology K.K.Leung Brain Research Centre,Fourth Military Medical University,Xi’an 710032,China

＜正＞Objective Motion sickness（MS） is considered as autonomic response to mismatched signals of visual,proprioceptive a nd vestibular organ,and abnormal vestibular information transmitted along both descending and ascending pathways plays a crucial role in inducing MS.Rats develope MS,as identified by pica when subjected to double rotation. To investigate the brain regions processing vestibular information.We performed immunohistochemistry for Fos protein and neuronal morphology studies after MS induced in rat subjected to motion.Methods Rats subjected to double axes rotation for 2 hours were divided into 5 experimental groups.Groups 1 to 3 were used for immunohistochemistry for Fos to detect activation of neurons in anterior cingulate cortex（ACC）,for consumption of kaolin,and for DiI labeling of ACC neurons,respectively.Results We observed（1） Fos-immunopostive neurons in ACC were significantly increased when compared to rats that were left beside the rotation apparatus（P＜0.05）;（2） average consumption of kaolin per day increased significantly post-rotation（by comparison of 4-day kaolin intake between pre- and post-rotation day）（P＜0.05）;and（3） density of dendritic spines（average number of spines along a secondary dendrite 10μm long ） increased significantly（P ＜0.05）.Conclusion Our data suggested that ACC is involved in processing of vestibular signals and that this brain region may likely participated in development of MS or some MS-related syndromes.

关键词： motion sickness Fos anterior cingulate cortex 1,1 ’-dioctadecyl-3 3,3’,3’-tetramethylindocarbocyanine perchlorate（DiI） rat

Activation of p38/MAPK in the anterior cingulate cortex contributes to pain-related negative emotion in rats

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Activation of p38/MAPK in the anterior cingulate cortex cont...

中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Hong CAO~(1,2),Gen-Cheng WU~2,Zhi-Qi ZHAO~1,Yu-Qiu ZHANG~1 1 Institute of Neurobiology 2 Department of Integrative Medicine and Neurobiology,Institutes of Brain Research and State Key Laboratory of Medical Neurobiology Shanghai Medical College,Fudan University,Shanghai 200032,China

＜正＞Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, including a sensory-discriminative and an emotional-affective component.Accumulating evidence from morphological, electrophysiological,neuroimaging,and behavioral studies as well as early clinical observation indicates that the anterior cingulate cortex（ACC） is involved in pain-related emotion.However,little is known about the molecular and cellular mechanisms underlying pain-related aversion in ACC.Our previous studies showed that NMDAR-dependent ERK signaling cascade in rat ACC contributes to pain emotion.In the present study we observed the role of p38,another member of MAP（mitogen-activated protein） kinase family,in ACC in pain-related negative emotion using Western Blot and behavioral training.Intra-plantar injection of 5%formalin produced a robust increase in phosphorylated MKK3/6（pMKK3/6）,upstream of p38/MAPK,and phosphorylated p38（p-p38） in the bilateral rostral ACC（rACC）.Using formalin-induced conditioned place avoidance（F-CPA） in rats,which is believed to reflect the pain-related negative emotion,we found that blockade of p38/MAPK activation in the rACC with p38 inhibitor SB203580（0.1μg,1μg per side） but not low dose（0.01μg per side）,or another kind of p38 inhibitor SB239063（0.1μg,1μg per side） dose-dependently prevented the induction of F-CPA.Interestingly,these blockades affected neither formalin-induced two-phase spontaneous pain nor low-intensity electric foot shock-induced CPA acquisition.Taken together,these results indicate that activation of p38/MAPK contributes to pain-related negative emotion,which will provide new molecule mechanisms underlying pain affect and bring new treatments for relieving emotional pain-related disturbance.

关键词： p38/MAPK formalin-induced conditioned place avoidance pain-related negative emotion anterior cingulate cortex rat

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

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

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 period.This 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 functions.However,it is still unknown whether this developmental neuroapoptosis affects the synaptic plasticity of the ACC in adulthood.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 exposure.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 slices.We found that the induction of LTP in the ACC was significantly reduced when compared to the control group.The 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 ACC.Thus,our present findings show that neonatal ketamine exposure causes a significant LTP impairment in the ACC.We 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