Synapse (New York, N.y.)最新文献_第7页

Postnatal and ovariectomic regulation of postsynaptic density protein-95 in the hippocampus of female Sprague-Dawley rats. 雌性Sprague-Dawley大鼠海马突触后密度蛋白-95的出生和卵巢切除调控。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2010-11-01 DOI: 10.1002/syn.20805

Dongmei Zhang, Jiqiang Zhang, Chen Bian, Qiyue Deng

{"title":"Postnatal and ovariectomic regulation of postsynaptic density protein-95 in the hippocampus of female Sprague-Dawley rats.","authors":"Dongmei Zhang, Jiqiang Zhang, Chen Bian, Qiyue Deng","doi":"10.1002/syn.20805","DOIUrl":"https://doi.org/10.1002/syn.20805","url":null,"abstract":"Postsynaptic density protein-95 (PSD-95) is hypothesized to control the excitatory-to-inhibitory ratio and plays an important role in the regulation of hippocampal synaptic plasticity, synaptogenesis, and learning and memory. In this report, we used immunoblotting to study the effects of aging and ovariectomy (OVX) on the expression of PSD-95 in the hippocampus of female rats. The results indicated that postnatal expression of hippocampal PSD-95 correlated with the fluctuation of circulating female sex hormones such as estrogen. Neonatal PSD-95 level was very low, but dramatically increased within the first month. The highest expression of PSD-95 was detected at postnatal day 30 (P30) and significantly decreased by 18 months. In the adult hippocampus, OVX significantly decreased PSD-95 expression within the first week, but it had recovered to adult levels 2 weeks later. Taken together, we conclude that circulating ovarian hormones may play a crucial role in the regulation of excitatory synapses within the hippocampus. Depletion of ovarian hormones can transiently and dramatically decrease the level of excitatory synapses for a limited time.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"875-8"},"PeriodicalIF":2.3,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20805","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40069842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Serotonin release variations during recovery of motor function after a spinal cord injury in rats. 大鼠脊髓损伤后运动功能恢复过程中血清素释放变化。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2010-11-01 DOI: 10.1002/syn.20802

Christine G Gerin, Angela Hill, Seritta Hill, Kristin Smith, Alain Privat

{"title":"Serotonin release variations during recovery of motor function after a spinal cord injury in rats.","authors":"Christine G Gerin, Angela Hill, Seritta Hill, Kristin Smith, Alain Privat","doi":"10.1002/syn.20802","DOIUrl":"https://doi.org/10.1002/syn.20802","url":null,"abstract":"Current literature suggests that serotonin (5-HT) release within the ventral horn of the spinal cord plays a role in motor function. We hypothesized that endogenous 5-HT release is involved in the recovery of motor function after spinal cord injury. To appreciate the functional parameters of regenerating serotonergic fibers, a microdialysis probe was stereotactically implanted in the ventral horn of subhemi-lesioned rats. Microdialysis in combination with HPLC was used to measure concentrations of 5-HT in the lumbar ventral horn during periods of rest (90 min), treadmill run (60 min) and postexercise rest (90 min) for a 1-month time period of recovery following the surgical lesion. Within the same period of time, 5-HT levels varied significantly. A significant (202%) increase was observed at day 18 postlesion relative to day 8, and a 16.4% decrease was observed at day 34 relative to day 18. Treadmill exercise challenge induced a 10% decrease of 5-HT release relative to rest at days 18 and 34. In conclusion, overtime treadmill locomotor recovery is parallel to amounts (rest basal levels) and patterns (exercise and postexercise levels) of 5-HT release suggesting that changes in serotonergic system occurred within the same time frame than locomotor recovery using treadmill challenge.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"855-61"},"PeriodicalIF":2.3,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20802","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40069839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 22

Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole. 芳香化酶在人脑中的独特分布:PET和[n -甲基- 11c]vorozole的体内研究。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2010-11-01 DOI: 10.1002/syn.20791

Anat Biegon, Sung Won Kim, David L Alexoff, Millard Jayne, Pauline Carter, Barbara Hubbard, Payton King, Jean Logan, Lisa Muench, Deborah Pareto, David Schlyer, Colleen Shea, Frank Telang, Gene-Jack Wang, Youwen Xu, Joanna S Fowler

{"title":"Unique distribution of aromatase in the human brain: in vivo studies with PET and [N-methyl-11C]vorozole.","authors":"Anat Biegon, Sung Won Kim, David L Alexoff, Millard Jayne, Pauline Carter, Barbara Hubbard, Payton King, Jean Logan, Lisa Muench, Deborah Pareto, David Schlyer, Colleen Shea, Frank Telang, Gene-Jack Wang, Youwen Xu, Joanna S Fowler","doi":"10.1002/syn.20791","DOIUrl":"https://doi.org/10.1002/syn.20791","url":null,"abstract":"Aromatase catalyzes the last step in estrogen biosynthesis. Brain aromatase is involved in diverse neurophysiological and behavioral functions including sexual behavior, aggression, cognition, and neuroprotection. Using positron emission tomography (PET) with the radiolabeled aromatase inhibitor [N-methyl-(11)C]vorozole, we characterized the tracer distribution and kinetics in the living human brain. Six young, healthy subjects, three men and three women, were administered the radiotracer alone on two separate occasions. Women were scanned in distinct phases of the menstrual cycle. Specificity was confirmed by pretreatment with a pharmacological (2.5 mg) dose of the aromatase inhibitor letrozole. PET data were acquired over a 90-min period and regions of interest placed over selected brain regions. Brain and plasma time activity curves, corrected for metabolites, were used to derive kinetic parameters. Distribution volume (V(T)) values in both men and women followed the following rank order: thalamus > amygdala = preoptic area > medulla (inferior olive) > accumbens, pons, occipital and temporal cortex, putamen, cerebellum, and white matter. Pretreatment with letrozole reduced V(T) in all regions, though the size of the reduction was region-dependent, ranging from ∼70% blocking in thalamus andpreoptic area to ∼10% in cerebellum. The high levels of aromatase in thalamus and medulla (inferior olive) appear to be unique to humans. These studies set the stage for the noninvasive assessment of aromatase involvement in various physiological and pathological processes affecting the human brain.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"801-7"},"PeriodicalIF":2.3,"publicationDate":"2010-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20791","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40069882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 100

Computational analysis of determinants of dopamine (DA) dysfunction in DA nerve terminals. 多巴胺神经末梢功能障碍决定因素的计算分析。

Synapse (New York, N.y.) Pub Date : 2009-12-01 DOI: 10.1002/syn.20686

Zhen Qi, Gary W Miller, Eberhard O Voit

{"title":"Computational analysis of determinants of dopamine (DA) dysfunction in DA nerve terminals.","authors":"Zhen Qi, Gary W Miller, Eberhard O Voit","doi":"10.1002/syn.20686","DOIUrl":"10.1002/syn.20686","url":null,"abstract":"Dopamine signaling is involved in a number of brain pathways, and its disruption has been suggested to be involved in the several disease states, including Parkinson's disease (PD), schizophrenia, and attention deficit hyperactivity disorder (ADHD). It has been hypothesized that altered storage, release, and reuptake of dopamine contributes to both the hypo- and hyperdopaminergic states that exist in various diseases. Here, we use our recently described mathematical model of dopamine metabolism, combined with a comprehensive Monte Carlo simulation analysis, to identify key determinants of dopamine metabolism associated with the dysregulation of dopamine homeostasis that may contribute to the pathogenesis of dopamine-based disorders. Our model reveals that the dopamine transporter (DAT), the vesicular monoamine transporter (VMAT2), and the enzyme monoamine oxidase (MAO) are the most influential components controlling the synaptic level of dopamine and the formation of toxic intracellular metabolites. The results are consistent with experimental observations and point to metabolic processes and combinations of processes that may be biochemical drivers of dopamine neuron degeneration. Since many of the identified components can be targeted therapeutically, the model may aid in the design of combined therapeutic regimens aimed at restoring proper dopamine signaling with toxic intermediates under control.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1133-42"},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759407/pdf/nihms133068.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40027181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Prenatal morphine exposure alters the layer II/III pyramidal neurons morphology in lateral secondary visual cortex of juvenile rats. 产前吗啡暴露改变幼鼠外侧第二视觉皮层第II/III层锥体神经元形态。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2009-12-01 DOI: 10.1002/syn.20694

Bin Mei, Lei Niu, Bin Cao, Dake Huang, Yifeng Zhou

{"title":"Prenatal morphine exposure alters the layer II/III pyramidal neurons morphology in lateral secondary visual cortex of juvenile rats.","authors":"Bin Mei, Lei Niu, Bin Cao, Dake Huang, Yifeng Zhou","doi":"10.1002/syn.20694","DOIUrl":"https://doi.org/10.1002/syn.20694","url":null,"abstract":"Altered cortical neuronal morphology and juvenile behavior manifestation by prenatal morphine exposure were well documented. However, this developmental morphine exposure affect the lateral secondary visual area (V2L), which may be critically involved in the multisensory of auditory and visual stimulus, remained poorly understood. To clarify the neuronal architecture changes possibly occurring in the V2L, Golgi-Cox staining was used in this study to count dendritic length and the spine density of the layer II/III pyramidal neurons in the V2L of the juvenile rats (postnatal day 25, PND25) prenatally exposed to morphine (gestation days 11-18). Quantitative analysis showed that prenatal morphine exposure decreased the total length, branch number, and spine density of the layer II/III pyramidal neurons in the V2L, and selectively altered the total length of the basal dendrites but not of the apical dendrites. The findings may provide the mechanistic understanding of the behavioral changes in the children whose mothers abuse opiates during pregnancy.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1154-61"},"PeriodicalIF":2.3,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20694","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40027176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Different mechanisms of Ca2+ regulation that influence synaptic transmission: comparison between crayfish and Drosophila neuromuscular junctions. 影响突触传递的Ca2+调节的不同机制:小龙虾和果蝇神经肌肉连接的比较。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2009-12-01 DOI: 10.1002/syn.20695

Mohati Desai-Shah, Robin L Cooper

{"title":"Different mechanisms of Ca2+ regulation that influence synaptic transmission: comparison between crayfish and Drosophila neuromuscular junctions.","authors":"Mohati Desai-Shah, Robin L Cooper","doi":"10.1002/syn.20695","DOIUrl":"https://doi.org/10.1002/syn.20695","url":null,"abstract":"A brief historical background on synaptic transmission in relation to Ca(2+) dynamics and short-term facilitation is described. This study focuses on the mechanisms responsible for the regulation of intracellular calcium concentration ([Ca(2+)](i)) in high output terminals of larval Drosophila compared to a low-output terminal of the crayfish neuromuscular junction (NMJ). Three processes; plasmalemmal Na(+)/Ca(2+) exchanger [NCX], Ca(2+)-ATPase (PMCA), and sarcoplasmic/endoplasmic Ca(2+)-ATPase (SERCA) are important in regulating the [Ca(2+)](i) are examined. When the NCX is compromised by reduced [Na(+)](o), no consistent effect occurred; but a NCX blocker KB-R7943 decreased the excitatory postsynaptic potential (EPSP) amplitudes. Compromising the PMCA with pH 8.8 resulted in an increase in EPSP amplitude but treatment with a PMCA specific inhibitor carboxyeosin produced opposite results. Thapsigargin exposure to block the SERCA generally decreases EPSP amplitude. Compromising the activity of the above Ca(2+) regulating proteins had no substantial effects on short-term depression. The Kum(170TS) strain (with dysfunctional SERCA), showed a decrease in EPSP amplitudes including the first EPSP within the train. Synaptic transmission is altered by reducing the function of the above three [Ca(2+)](i) regulators; but they are not consistent among different species as expected. Results in crayfish NMJ were more consistent with expected results as compared to the Drosophila NMJ. It is predicated that different mechanisms are used for regulating the [Ca(2+)](i) in high and low output synaptic terminals.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1100-21"},"PeriodicalIF":2.3,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20695","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40007468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 23

Inverse agonist histamine H3 receptor PET tracers labelled with carbon-11 or fluorine-18. 用碳-11或氟-18标记的组胺H3受体PET示踪剂。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2009-12-01 DOI: 10.1002/syn.20689

Terence G Hamill, Nagaaki Sato, Makoto Jitsuoka, Shigeru Tokita, Sandra Sanabria, Waisi Eng, Christine Ryan, Stephen Krause, Norihiro Takenaga, Shil Patel, Zhizhen Zeng, David Williams, Cyrille Sur, Richard Hargreaves, H Donald Burns

{"title":"Inverse agonist histamine H3 receptor PET tracers labelled with carbon-11 or fluorine-18.","authors":"Terence G Hamill, Nagaaki Sato, Makoto Jitsuoka, Shigeru Tokita, Sandra Sanabria, Waisi Eng, Christine Ryan, Stephen Krause, Norihiro Takenaga, Shil Patel, Zhizhen Zeng, David Williams, Cyrille Sur, Richard Hargreaves, H Donald Burns","doi":"10.1002/syn.20689","DOIUrl":"https://doi.org/10.1002/syn.20689","url":null,"abstract":"Two histamine H3 receptor (H3R) inverse agonist PET tracers have been synthesized and characterized in preclinical studies. Each tracer has high affinity for the histamine H3 receptor, has suitable lipophilicity, and neither is a substrate for the P-glycoprotein efflux pump. A common phenolic precursor was used to synthesize each tracer with high specific activity and radiochemical purity by an alkylation reaction using either [(11)C]MeI or [(18)F]FCD(2)Br. Autoradiographic studies in rhesus monkey and human brain slices showed that each tracer had a widespread distribution with high binding densities in frontal cortex, globus pallidus and striatum, and lower uptake in cerebellum. The specificity of this expression pattern was demonstrated by the blockade of the autoradiographic signal by either the H3R agonist R-alpha-methylhistamine or a histamine H3R inverse agonist. In vivo PET imaging studies in rhesus monkey showed rapid uptake of each tracer into the brain with the same distribution seen in the autoradiographic studies. Each tracer could be blocked by pretreatment with a histamine H3R inverse agonist giving a good specific signal. Comparison of the in vitro metabolism of each compound showed slower metabolism in human liver microsomes than in rhesus monkey liver microsomes, with each compound having a similar clearance rate in humans. The in vivo metabolism of 1b in rhesus monkey showed that at 60 min, approximately 35% of the circulating counts were due to the parent. These tracers are very promising candidates as clinical PET tracers to both study the histamine H3R system and measure receptor occupancy of H3R therapeutic compounds.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1122-32"},"PeriodicalIF":2.3,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40027175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 39

Decreased dendritic spine density of neurons of the prefrontal cortex and nucleus accumbens and enhanced amphetamine sensitivity in postpubertal rats after a neonatal amygdala lesion. 新生儿杏仁核损伤后青春期后大鼠前额皮质和伏隔核神经元树突棘密度降低，安非他明敏感性增强。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2009-12-01 DOI: 10.1002/syn.20697

Oscar Solis, Rubén Antonio Vázquez-Roque, Israel Camacho-Abrego, Citlalli Gamboa, Fidel De La Cruz, Sergio Zamudio, Gonzalo Flores

{"title":"Decreased dendritic spine density of neurons of the prefrontal cortex and nucleus accumbens and enhanced amphetamine sensitivity in postpubertal rats after a neonatal amygdala lesion.","authors":"Oscar Solis, Rubén Antonio Vázquez-Roque, Israel Camacho-Abrego, Citlalli Gamboa, Fidel De La Cruz, Sergio Zamudio, Gonzalo Flores","doi":"10.1002/syn.20697","DOIUrl":"https://doi.org/10.1002/syn.20697","url":null,"abstract":"A neonatal basolateral-amygdala (nBLA) lesion in rats could be a potential animal model to study the early neurodevelopmental abnormalities associated with the behavioral and morphological brain changes observed in schizophrenia. Morphological alterations in pyramidal neurons from the prefrontal cortex (PFC) have been observed in postmortem schizophrenic brains, mainly because of decreased dendritic arbor and spine density. We assessed the effects of nBLA-lesion on the dendritic morphology of neurons from the PFC and the nucleus accumbens (NAcc) in rats. nBLA lesions were made on postnatal day 7 (PD7), and later, the dendritic morphology was studied by the Golgi-Cox stain procedure followed by Sholl analysis at PD35 (prepubertal) and PD60 (adult) ages. We also evaluated the effects of the nBLA-lesion on locomotor activity caused by a novel environment, apomorphine, and amphetamine. Adult animals with nBLA lesions showed a decreased spine density in pyramidal neurons from the PFC and in medium spiny cells from the NAcc. An increased locomotion in a novel environment and in amphetamine-treated adult animals with an nBLA-lesion was observed. Our results indicate that nBLA-lesion alters the neuronal dendrite morphology of the NAcc and PFC, suggesting a disconnection between these limbic structures. The locomotion paradigms support the idea that dopaminergic transmission is altered in the nBLA lesion model. This could help to understand the consequences of an earlier amygdala dysfunction in schizophrenia.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"1143-53"},"PeriodicalIF":2.3,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20697","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40027177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 33

SV2 frustrating exocytosis at the semi-diffusor synapse. SV2抑制半扩散突触的胞吐作用。

IF 2.3

Synapse (New York, N.y.) Pub Date : 2009-04-01 DOI: 10.1002/syn.20610

Jean Vautrin

{"title":"SV2 frustrating exocytosis at the semi-diffusor synapse.","authors":"Jean Vautrin","doi":"10.1002/syn.20610","DOIUrl":"https://doi.org/10.1002/syn.20610","url":null,"abstract":"Presynaptic exocytosis is the mechanism commonly believed to release transmitters by diffusion through a pore opening during vesicular membrane fusion with the plasmalemma, but evidence suggesting that exocytosis and transmitter release are two separate steps of synaptic transmission is accumulating. Vesicular glycoconjugates such as Synaptic Vesicle Protein 2 (SV2) proteoglycans and gangliosides retain transmitters in a nondiffusible form and are transported to the synaptic cleft where they contribute forming a dense synaptomatrix. Transmitters are permanently present in synaptic clefts and readily releasable transmitter is easily accessible from the outer side of the presynaptic membrane suggesting that synaptomatrix glycoconjugates prevent immediate release after PKC-dependent exocytosis. The calcium sensor synaptotagmin is also present at the presynaptic plasma membrane and binds SV2 suggesting a direct coupling between the calcium transient and transmitter release from the synaptomatrix. A quantitative coupling of the cytosolic calcic transient to transmitter release from the synaptomatrix explains better complexity and plasticity of miniature postsynaptic signals hitherto difficult to account for in exocytic terms. This alternative representation of synaptic transmission in which the same components of the synaptomatrix support adhesion and signaling functions may cast new lights on synaptic diseases such as Alzheimer's disease.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"319-38"},"PeriodicalIF":2.3,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/syn.20610","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39988739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 17

Cholinergic direct inhibition of N-methyl-D aspartate receptor-mediated currents in the rat neocortex. 胆碱能直接抑制n -甲基- d天冬氨酸受体介导的大鼠新皮层电流。

Synapse (New York, N.y.) Pub Date : 2009-04-01 DOI: 10.1002/syn.20609

Jorge Flores-Hernandez, Humberto Salgado, Victor De La Rosa, Tania Avila-Ruiz, Oswaldo Torres-Ramirez, Gustavo Lopez-Lopez, Marco Atzori

{"title":"Cholinergic direct inhibition of N-methyl-D aspartate receptor-mediated currents in the rat neocortex.","authors":"Jorge Flores-Hernandez, Humberto Salgado, Victor De La Rosa, Tania Avila-Ruiz, Oswaldo Torres-Ramirez, Gustavo Lopez-Lopez, Marco Atzori","doi":"10.1002/syn.20609","DOIUrl":"10.1002/syn.20609","url":null,"abstract":"Acetylcholine (ACh) and N-methyl-D aspartate receptors (NMDARs) interact in the regulation of multiple important brain functions. NMDAR activation is indirectly modulated by ACh through the activation of muscarinic or nicotinic receptors. Scant information is available on whether ACh directly interacts with the NMDAR. By using a cortical brain slice preparation we found that the application of ACh and of other drugs acting on muscarinic or nicotinic receptors induces an acute and reversible reduction of NMDAR-mediated currents (I(NMDA)), ranging from 20 to 90% of the control amplitude. The reduction displayed similar features in synaptic I(NMDA) in brain slices, as well as in currents evoked by NMDA application in brain slices or from acutely dissociated cortical cells, demonstrating its postsynaptic nature. The cholinergic inhibition of I(NMDA) displayed an onset-offset rate in the order of a second, and was resistant to the presence of the muscarinic antagonist atropine (10 microM) in the extracellular solution, and of G-protein blocker GDP(beta)S (500 microM) and activator GTP(gamma)S (400 microM) in the intracellular solution, indicating that it was not G-protein dependent. Recording at depolarized or hyperpolarized holding voltages reduced NMDAR-mediated currents to similar extents, suggesting that the inhibition was voltage-independent, whereas the reduction was markedly more pronounced in the presence of glycine (20 microM). A detailed analysis of the effects of tubocurarine suggested that at least this drug interfered with glycine-dependent NMDAR-activity. We conclude that NMDAR-mediated current scan be inhibited directly by cholinergic drugs, possibly by direct interaction within one or more subunits of the NMDAR. Our results could supply a new interpretation to previous studies on the role of ACh at the glutamatergic synapse.","PeriodicalId":118978,"journal":{"name":"Synapse (New York, N.y.)","volume":" ","pages":"308-18"},"PeriodicalIF":0.0,"publicationDate":"2009-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836798/pdf/nihms-133067.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39988740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0