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Whole-Brain Direct Inputs to and Axonal Projections from excitatory and Inhibitory Neurons in the Mouse Primary Auditory Area

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Neuroscience Bulletin 2022年第6期38卷 576-590页

作者： Mengting Zhao Miao Ren Tao Jiang Xueyan Jia Xiaojun Wang Anan Li Xiangning Li Qingming Luo Hui Gong Briton Chance Center for Biomedical Photonics Wuhan National Laboratory for OptoelectronicsMoE Key Laboratory for Biomedical PhotonicsHuazhong University of Science and TechnologyWuhan 430074China Key Laboratory of Biomedical Engineering of Hainan Province School of Biomedical EngineeringHainan UniversityHaikou 570228China HUST-Suzhou Institute for Brainsmatics JITRISuzhou 215123China

Neurons in the primary auditory area(AUDp)innervate multiple brain regions with long-range projections while receiving informative inputs for diverse functions.However,the brain-wide connections of these neurons have not been comprehensively investigated.Here,we simultaneously applied virus-based anterograde and retrograde tracing,labeled the connections of excitatory and inhibitory neurons in the mouse AUDp,and acquired whole-brain information using a dual-channel fuorescence micro-optical sectioning tomography system.Quantified results showed that the two types of neurons received inputs with similar patterns but sent heterogeneous projections to downstream regions.In the isocortex,functionally different areas consistently sent feedback-dominated projections to these neurons,with concomitant laterallydominated projections from the sensory and limbic cortices to inhibitory neurons.In subcortical regions,the dorsal and medial parts of the non-lemniscal auditory thalamus(AT)were reciprocally connected to the AUDp,while the ventral part contained the most fibers of passage from the excitatory neurons and barely sent projections back,indicating the regional heterogeneity of the AUDp-AT circuit.Our results reveal details of the whole-brain network and provide new insights for further physiological and functional studies of the AUDp.

关键词： Primary auditory area excitatory Inhibitory Direct inputs Axonal projections

Absence of interleukin-1 receptor 1 increases excitatory and inhibitory scaffolding protein expression and microglial activation in the adult mouse hippocampus

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Cellular & Molecular Immunology 2015年第5期12卷 645-647页

作者： Una Avdic Deepti Chugh Harer Osman Katie Chapman Johanna Jackson Christine T Ekdahl Inflammation and Stem Cell Therapy Group Division of Clinical Neurophysiology Lund University Lund Sweden Lund Epilepsy Center Lund University Lund Sweden Current address: Division of Neurology Department of Clinical Sciences Lund University Lund Sweden Current address: Lilly UK Windlesham Surrey UK

In the present study, we demonstrate that adult mice lacking interleukin- 1 receptor 1 （IL- 1R1） exhibit increased express- ion of both the excitatory scaffolding protein postsynaptic density-95 （PSD-95） and inhibitory scaffolding proteinge- phyrin, respectively, in the hippocampus. The morphology of hippocampal microglia is also altered towards a more activated phenotype. These results indicate an important role for IL-1 signaling in maintaining physiological conditions in both neurons and microglia.

关键词： increases excitatory inhibitory scaffolding

Rac1 Modulates excitatory Synaptic Transmission in Mouse Retinal Ganglion Cells

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Neuroscience Bulletin 2019年第4期35卷 673-687页

作者： Ling-Zhu Li Ning Yin Xue-Yan Li Yanying Miao Shuo Cheng Fang Li Guo-Li Zhao Shu-Min Zhong Xin Wang Xiong-Li Yang Zhongfeng Wang Department of Neurology Institutes of Brain Science State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Zhongshan Hospital Fudan University

Ras-related C3 botulinum toxin substrate 1(Racl),a member of the Rho GTPase family which plays important roles in dendritic spine morphology and plasticity,is a key regulator of cytoskeletal reorganization in dendrites and spines.Here,we investigated whether and how Racl modulates synaptic transmission in mouse retinal ganglion cells(RGCs)using selective conditional knockout of Racl(Racl-cKO).Racl-cKO significantly reduced the frequency of AMPA receptor-mediated miniature excitatory postsynaptic currents,while glycine/GABA_A receptor-mediated miniature inhibitory postsynaptic currents were not affected.Although the total GluA1 protein level was increased in Racl-cKO mice,its expression in the membrane component was unchanged.RaclcKO did not affect spine-like branch density in single dendrites,but significantly reduced the dendritic complexity,which resulted in a decrease in the total number of dendritic spine-like branches.These results suggest that Racl selectively affects excitatory synaptic transmission in RGCs by modulating dendritic complexity.

关键词： Rac1 Retinal ganglion cell excitatory synaptic transmission Dendrite Dendritic spine

Non-cholinergic late slow excitatory postsynaptic potential, 5-hydroxytryptamine and substance P

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Chinese Science Bulletin 1996年第9期41卷 762-765页

作者：孔德虎黄振信马如纯蔡圣荣裴文芬 Department of Physiology Anhui Medical University Hefei 230032 China Department of Physiology Anhui Chinese Traditional Med. Coll. Hefei 230038 China

It has been recognized that substance P (SP) and 5-hydroxytryptamine (5-HT) maybe the transmitters mediating non-cholinergic late slow excitatory postsynaptic potential(LS-EPSP) in the neurons of guinea pig inferior m... 详细信息

关键词： late slow excitatory postsynaptic potential 5-hydroxytryptamine substance P inferior mesenteric ganglion.

excitatory amino acids in cerebrospinal fluid and their relations with clinical features and outcomes in acute head injury

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Chinese Medical Journal 1998年第11期 19-22页

作者：张新定裘明德张星虎张建生张虹康笃伦

Abstract Objective To determine the contents and dynamics of excitatory amino acids (EAAs), glutamate (GLU) and aspartate (ASP) in the cerebrospinal fluid (CSF) of patients with acute head injury and to clarify the relationship of EAAs with clinical features and outcomes. Methods Forty two adults with acute head injury were included. Glasgow coma scale (GCS) obtained at admission and Glasgow outcome scale (GOS) obtained three months post injury were assessed. Samples of CSF were obtained via ventricular or lumbar puncture every 24 hours. GLU and ASP in CSF were analyzed by reversed phase HPLC with a fluorescent detector. Nine control subjects were adults with lumbar anesthesia but without neurological diseases. Results The peak concentration of GLU and ASP of head injured group was significantly higher than that of the control group. Dynamic research on severely injured ones indicated that the peak value of GLU mostly appeared within 48 hours post injury; it decreased with the improving or remaining of the neurological status, and increased with the deterioration, but was still higher than that of the control seven days post injury. The peak value of EAAs of severely injured patients was conspicuously higher than that of mildly injured group. There was a significant negative correlation between the peak values of GCS and EAAs. The peak value of EAAs in patients with poor outcome was remarkably higher than that in patients with good outcome. GOS was closely correlated to the peak value of EAAs. When the concentration of GLU was over 7 μmol/L, the rate of poor outcome increased markedly. Conclusion The content of EAAs in CSF increases following acute head injury and remains higher at least a week post injury in severely injured patients. The more severe the trauma, the more obvious the excitotoxicity induced by EAAs; the more serious the secondary brain insult and the brain edema will be, the worse the outcome, naturally.

关键词： injury head acids excitatory

Chronic Intermittent Hypobaric Hypoxia Ameliorates Renal Vascular Hypertension Through Up-regulating NOS in Nucleus Tractus Solitarii

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Neuroscience Bulletin 2019年第1期35卷 79-90页

作者： Na Li Yue Guan Yan-Ming Tian Hui-Jie Ma Xiangjian Zhang Yi Zhang Sheng Wang Department of Physiology Hebei Medical UniversityShijiazhuang 050017China Department of Physiology Basic Medical CollegeHebei UniversityBaoding 071000China Hebei Collaborative Innovation Center for Cardio-cerebrovascular Disease Shijiazhuang 050000China

Chronic intermittent hypobaric hypoxia(CIHH)is known to have an anti-hypertensive effect, which might be related to modulation of the baroreflex in rats with renal vascular hypertension(RVH). In this study, RVH was induced by the 2-kidney-1-clip method(2 K1 C) in adult male Sprague-Dawley rats. The rats were then treated with hypobaric hypoxia simulating 5000 m altitude for 6 h/day for 28 days. The arterial blood pressure(ABP), heart rate(HR), and renal sympathetic nerve activity(RSNA) were measured before and after microinjection of L-arginine into the nucleus tractus solitarii(NTS) in anesthetized rats.Evoked excitatory postsynaptic currents(eEPSCs) and spontaneous EPSCs(sEPSCs) were recorded in anterogradely-labeled NTS neurons receiving baroreceptor afferents. We measured the protein expression of neuronal nitric oxide synthase(nNOS) and endothelial NOS(eNOS) in the NTS. The results showed that the ABP in RVH rats was significantly lower after CIHH treatment. The inhibition of ABP, HR, and RSNA induced by L-arginine was less in RVH rats than in sham rats, and greater in the CIHHtreated RVH rats than the untreated RVH rats. The eEPSC amplitude in NTS neurons receiving baroreceptor afferents was lower in the RVH rats than in the sham rats and recovered after CIHH. The protein expression of nNOS and e NOS in the NTS was lower in the RVH rats than in the sham rats and this decrease was reversed by CIHH. In short, CIHH treatment decreases ABP in RVH rats via upregulating NOS expression in the NTS.

关键词： Chronic intermittent hypobaric hypoxia Renal vascular hypertension Nitric oxide Renal sympathetic nerve activity excitatory postsynaptic current

Contribution of Baroreflex Afferent Pathway to NPY-Mediated Regulation of Blood Pressure in Rats

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Neuroscience Bulletin 2020年第4期36卷 396-406页

作者： Yang Liu Shu-Yang Zhao Yan Feng Jie Sun Xiao-Long Lu Qiu-Xin Yan Ying Li Zhuo Liu Lu-Qi Wang Xun Sun Shijun Li Guo-Fen Qiao Bai-Yan Li Department of Pharmacology State-Province Key Laboratories of Biomedicine-Pharmaceutics of ChinaKey Laboratory of Cardiovascular Medicine ResearchMinistry of EducationCollege of PharmacyHarbin Medical UniversityHarbin 150081China Department of Clinical Laboratory The First Affiliated Hospital of Dalian Medical UniversityDalian 116011China Department of Pharmacology College of PharmacyDalian Medical UniversityDalian 116044China Riley Heart Center Wells Center for Pediatric ResearchIndiana University School of MedicineIndianapolisIN 46202USA

Neuropeptide Y (NPY), a metabolism-related cardiovascular factor, plays a crucial role in blood pressure(BP) regulation via peripheral and central pathways. The expression of NPY receptors (Y1R/Y2R) specific to baroreflex afferents impacts on the sexually dimorphic neural control of circulation. This study was designed to investigate the expression profiles of NPY receptors in the nodose ganglion (NG) and nucleus tractus solitary (NTS) under hypertensive conditions. To this end, rats with hypertension induced by NG-nitro-L-arginine methylester (L-NAME) or high fructose drinking (HFD), and spontaneously hypertensive rats (SHRs) were used to explore the effects/mechanisms of NPY on BP using functional, molecular, and electrophysiological approaches. The data showed that BP was elevated along with baroreceptor sensitivity dysfunction in model rats;Y1R was up-or down-regulated in the NG or NTS of male and female HFD/L-NAME groups,while Y2R was only down-regulated in the HFD groups as well as in the NG of the male L-NAME group. In SHRs,Y1R and Y2R were both down-regulated in the NTS, and not in the NG. In addition to NPY-mediated energy homeostasis, leptin-melanocortin activation may be essential for metabolic disturbance-related hypertension. We found that leptin and a-melanocyte stimulating hormone (aMSH) receptors were aberrantly down-regulated in HFD rats. In addition, a-MSH concentrations were reduced and NPY concentrations were elevated in the serum and NTS at 60 and 90 min after acute leptin infusion. Electrophysiological recordings showed that the decay time-constant and area under the curve of excitatory post-synaptic currents were decreased by Y1R activation in A-types, whereas, both were increased by Y2R activation in Ah-or C-types. These results demonstrate that sex-and afferent-specific NPY receptor expression in the baroreflex afferent pathway is likely to be a novel target for the clinical management of metabolism-related and essential hypertension.

关键词： Neuropeptide Y Hypertension Nucleus of the solitary tract excitatory post-synaptic current Baroreflex

Glutamate transporters, EAAT1 and EAAT2, are potentially important in the pathophysiology and treatment of schizophrenia and affective disorders

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World Journal of Psychiatry 2018年第2期8卷 51-63页

作者： Georgia M Parkin Madhara Udawela Andrew Gibbons Brian Dean Molecular Psychiatry Laboratory the Florey Institute of Neuroscience and Mental Health CRC for Mental Health Research Centre for Mental Health the Faculty of Health Arts and Design Swinburne University

Glutamate is the predominant excitatory neurotransmitter in the human brain and it has been shown that prolonged activation of the glutamatergic system leads to nerve damage and cell death. Following release from the pre-synaptic neuron and synaptic transmission, glutamate is either taken up into the presynaptic neuron or neighbouring glia by transmembrane glutamate transporters. excitatory amino acid transporter(EAAT) 1 and EAAT2 are Na+-dependant glutamate transporters expressed predominantly in glia cells of the central nervous system. As the most abundant glutamate transporters, their primary role is to modulate levels of glutamatergic excitability and prevent spill over of glutamate beyond the synapse. This role is facilitated through the binding and transportation of glutamate into astrocytes and microglia. The function of EAAT1 and EAAT2 is heavily regulated at the levels of gene expression, post-transcriptional splicing, glycosylation states and cell-surface trafficking of the protein. Both glutamatergic dysfunction and glial dysfunction have been proposed to be involved in psychiatric disorder. This review will present an overview of the roles that EAAT1 and EAAT2 play in modulating glutamatergic activity in the human brain, and mount an argument that these two transporters could be involved in the aetiologies of schizophrenia and affective disorders as well as represent potential drug targets for novel therapies for those disorders.

关键词： Glia excitatory amino acid transporter Psychiatry Affective disorders Glutamate transporter Glutamate Schizophrenia

excitatory amino acid on secondary spinal cord injury: effect anmechanism

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Journal of Medical Colleges of PLA(China) 1996年第4期11卷 274-277页

作者：叶晓健李家顺王家林李明

Ｅｘｃｉｔａｔｏｒｙａｍｉｎｏａｃｉｄｏｎｓｅｃｏｎｄａｒｙｓｐｉｎａｌｃｏｒｄｉｎｊｕｒｙ：ｅｆｆｅｃｔａｎｍｅｃｈａｎｉｓｍ￥（叶晓健）（李家顺）（王家林），（李明）ＹｅＸｉａｏｊｉａｎ，ＬｉＪｉａｓｈｕｎ，Ｗａ... 详细信息

Ｅｘｃｉｔａｔｏｒｙａｍｉｎｏａｃｉｄｏｎｓｅｃｏｎｄａｒｙｓｐｉｎａｌｃｏｒｄｉｎｊｕｒｙ：ｅｆｆｅｃｔａｎｍｅｃｈａｎｉｓｍ￥（叶晓健）（李家顺）（王家林），（李明）ＹｅＸｉａｏｊｉａｎ，ＬｉＪｉａｓｈｕｎ，ＷａｎｇＪｉａｌｉｎＬｉＭｉｎｇ（Ｄｅ...

关键词： spinal cord injury excitatory arnino acid NMDA receptor antagonist