On the Respective Roles of Nitric Oxide and Carbon Monoxide in Long-Term Potentiation in the Hippocampus

Perfusion of hippocampal slices with an inhibitor of nitric oxide (NO) synthase-blocked induction of long-term potentiation (LTP) produced by a one-train tetanus and significantly reduced LTP by a two-train tetanus, but only slightly reduced LTP by a four-train tetanus. Inhibitors of heme oxygenase, the synthetic enzyme for carbon monoxide (CO), significantly reduced LTP by either a two-train or four-train tetanus. These results suggest that NO and CO are both involved in LTP but may play somewhat different roles. One possibility is that NO serves a phasic, signaling role, whereas CO provides tonic, background stimulation. Another possibility is that NO and CO are phasically activated under somewhat different circumstances, perhaps involving different receptors and second messengers. Because NO is known to be activated by stimulation of NMDA receptors during tetanus, we investigated the possibility that CO might be activated by stimulation of metabotropic glutamate receptors (mGluRs). Consistent with this idea, long-lasting potentiation by the mGluR agonist tACPD was blocked by inhibitors of heme oxygenase but not NO synthase. Potentiation by tACPD was also blocked by inhibitors of soluble guanylyl cyclase (a target of both NO and CO) or cGMP-dependent protein kinase, and guanylyl cyclase was activated by tACPD in hippocampal slices. However, biochemical assays indicate that whereas heme oxygenase is constitutively active in hippocampus, it does not appear to be stimulated by either tetanus or tACPD. These results are most consistent with the possibility that constitutive (tonic) rather than stimulated (phasic) heme oxygenase activity is necessary for potentiation by tetanus or tACPD, and suggest that mGluR activation stimulates guanylyl cyclase phasically through some other pathway.     

Inhibition of the Endothelial Isoform of Nitric Oxide Synthase Impairs Long-Term Memory Formation in the Chick

Previous studies with general inhibitors of nitric oxide synthase have yielded variable and contradictory results with respect to their effects on memory. This may have been due to differential effects of blocking the various isoforms of this enzyme. We show that day-old chicks trained on a single-trial passive-avoidance task suffered significant memory loss from ~40 min post-training following post-training intracranial administration of a potent inhibitor of eNOS. Administration of a specific nNOS or iNOS inhibitor at the same time had no effect on retention, although a role for either of these isoforms when administered at a different time after learning has yet to be fully investigated. The onset of memory loss following eNOS inhibition is the same as observed following general NOS inhibition, which suggests that amnestic effects observed in previous studies using nonspecific inhibitors may be attributable to blocking the function of eNOS. The findings indicate that eNOS may play a role in memory formation for this task, which is at least distinct from any role that may be played by nNOS.     

Neuronal NT-3 Is not Required For Synaptic Transmission or Long-Term Potentiation in Area CA1 of the Adult Rat Hippocampus

Neurotrophic factors, including BDNF and NT-3, have been implicated in the regulation of synaptic transmission and plasticity. Previous attempts to analyze synaptic transmission and plasticity in mice lacking the NT-3 gene have been hampered by the early death of the NT-3 homozygous knockout animals. We have bypassed this problem by examining synaptic transmission in mice in which the NT-3 gene is deleted in neurons later in development, by crossing animals expressing the CRE recombinase driven by the synapsin I promoter to animals in which the NT-3 gene is floxed. We conducted blind field potential recordings at the Schaffer collateral–CA1 synapse in hippocampal slices from homozygous knockout and wild-type mice. We examined the following indices of synaptic transmission: (1) input-output relationship; (2) paired-pulse facilitation; (3) post-tetanic potentiation; and (4) long-term potentiation: induced by two different protocols: (a) two trains of 100-Hz stimulation and (b) theta burst stimulation. We found no difference between the knockout and wild-type mice in any of the above measurements. These results suggest that neuronal NT-3 does not play an essential role in normal synaptic transmission and some forms of plasticity in the mouse hippocampus.     

Impaired Memory Retention and Decreased Long-Term Potentiation in Integrin-Associated Protein-Deficient Mice

Previously, we have demonstrated that integrin-associated protein (IAP) mRNA level is approximately fourfold higher in rats showing good retention performance (600 sec) than rats showing poor retention performance (<80 sec) in an inhibitory avoidance learning paradigm. In the present study, we have used the gene-targeted IAP-deficient mice to further investigate the role of IAP involved in memory formation and hippocampal long-term potentiation (LTP) in vivo. Results revealed that there was a significant impairment in memory retention and a significant reduction in the magnitude of LTP in IAP-deficient mice when compared with the wild-type and heterozygote mice, whereas the wild-type and heterozygote animals did not show marked differences on these measures. Furthermore, the impairment in retention performance of IAP-deficient mice was not due to different sensitivities of these animals to the electric shock. When we examined locomotor activity and rotarod treadmill performance, no differences were observed among these three groups of animals either. Western blot analysis confirmed the lack of IAP protein in IAP-deficient mice, whereas IAP expression was similar in both the wild-type and heterozygote controls. These results together demonstrate that IAP plays an important role in the process of memory formation and synaptic plasticity in mice.     

诱导性一氧化氮合酶在动脉硬化中的作用

动脉硬化是心脑血管疾病的基础,严重危害人类健康的脑血栓,脑出血以及冠心病的发生都和动脉硬化有着密切的联系.近年来随着对动脉硬化发生机制的研究,诱导性一氧化氮合酶越来越受到关注,其和动脉硬化发生的关系已不客忽视.本文就诱导性一氧化氮合酶和动脉硬化的关系作简要介绍.     

Selective Abolition of the NMDA Component of Long-Term Potentiation in Mice Lacking mGluR5

The mechanisms underlying the differential expression of long-term potentiation (LTP) by AMPA and NMDA receptors, are unknown, but could involve G-protein-linked metabotropic glutamate receptors. To investigate this hypothesis we created mutant mice that expressed no metabotropic glutamate receptor 5 (mGluR5), but showed normal development. In an earlier study of these mice we analyzed field-excitatory postsynaptic potential (fEPSPs) in CA1 region of the hippocampus and found a small decrease; possibly arising from changes in the NMDAR-mediated component of synaptic transmission. In the present study we used whole-cell patch clamp recordings of evoked excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons to identify the AMPAR- and NMDAR-mediated components of LTP. Recordings from control mice following tetanus, or agonist application (IS, 3R-1-amino-cyclopentane 1,3-dicarboxylic acid) (ACPD), revealed equal enhancement of the AMPA and NMDA receptor-mediated components. In contrast, CA1 neurons from mGluR5-deficient mice showed a complete loss of the NMDA-receptor-mediated component of LTP (LTP_NMDA), but normal LTP of the AMPA-receptor-mediated component (LTP_AMPA). This selective loss of LTP_NMDA was seen in three different genotypic backgrounds and was apparent at all holding potentials (−70 mV to +20 mV). Furthermore, the LTP_NMDA deficit in mGluR5 mutant mice could be rescued by stimulating protein kinase C (PKC) with 4β-phorbol-12,13-dibutyrate (PDBu). These results suggest that PKC may couple the postsynaptic mGluR5 to the NMDA-receptor potentiation during LTP, and that this signaling mechanism is distinct from LTP_AMPA. Differential enhancement of AMPAR and NMDA receptors by mGluR5 also supports a postsynaptic locus for LTP.     

诱导性一氧化氮合酶在动脉硬化中的作用

动脉硬化是心脑血管疾病的基础,严重危害人类健康的脑血栓,脑出血以及冠心病的发生都和动脉硬化有着密切的联系。近年来随着对动脉硬化发生机制的研究,诱导性一氧化氮合酶越来越受到关注,其和动脉硬化发生的关系已不容忽视。本文就诱导性一氧化氮合酶和动脉硬化的关系作简要介绍。     

一氧化氮在新生儿缺氧缺血性脑病中的作用

在围产期窒息引起的新生儿缺氧缺血性脑病（HIE）中,一氧化氮（NO）对脑组织具有神经保护性和神经毒性双重效应,这取决于NO的来源。并且NO与谷氨酸及内皮素（ET）相互作用。应用哲学观点深入研究NO的作用机制对于探讨HIE的防治具有重要意义。     

一氧化氮在支气管哮喘中的作用

一氧化氮是一种具有广泛并且复杂生物活性的小分子化合物,参与多种病理生理过程.众多研究表明,其在支气管哮喘的发病机制中有着多种复杂的双相调节作用.本文通过对一氧化氮在支气管哮喘发病机制中的调节作用研究的历史回顾和现状的阐述,探讨辩证法与系统论在科学研究中的应用.     

一氧化氮在支气管哮喘中的作用

一氧化氮是一种具有广泛并且复杂生物活性的小分子化合物,参与多种病理生理过程。众多研究表明,其在支气管哮喘的发病机制中有着多种复杂的双相调节作用。本文通过对一氧化氮在支气管哮喘发病机制中的调节作用研究的历史回顾和现状的阐述,探讨辩证法与系统论在科学研究中的应用。     

一氧化氮在新生儿缺氧缺血性脑病中的作用

在围产期窒息引起的新生儿缺氧缺血性脑病(HIE)中,一氧化氮(NO)对脑组织具有神经保护性和神经毒性双重效应,这取决于NO的来源.并且NO与谷氨酸及内皮素(ET)相互作用.应用哲学观点深入研究NO的作用机制对于探讨HIE的防治具有重要意义.     

Interference Between Location and Distance Information in Motor Short-Term Memory: The Respective Roles of Direct Kinesthetic Signals and Abstract Codes

Interference between location and distance information in motor short-term memory has been hypothesized on the basis of the systematic pattern of undershooting and overshooting in movement reproduction that occurs when the starting position for reproduction movements is shifted. To determine the possible contribution of limb-specific kinesthetic information to this systematic undershooting-overshooting pattern, we compared the reproduction of linear arm positioning movements performed under either same-limb or switched-limb conditions. Ten subjects were assigned to either a location or distance cue condition, and each subject completed a total of 40 trials, 20 under same-limb and 20 under switched-limb conditions. Each trial consisted of criterion and reproduction movements, separated by a 10-s retention interval. The starting position for the reproduction movement was shifted by 0, 2, or 4 cm in either direction from that of the criterion movement. The systematic undershooting-overshooting pattern, which occurs when either the movement location or distance is reproduced, arose under both the same-limb and switched-limb conditions, suggesting that the primary cause of the location-distance interference is not limb-specific kinesthetic information. Rather, more abstract information in the form of a conceptual memory code appears to be the probable cause of the location distance interference phenomenon.     

自我概念长时记忆表征的性别特征:自我参照实验范式的检验

记忆的自我参照效应实验范式,常被用来探讨自我概念长时记忆表征问题。不同于以往研究,本研究将作为记忆材料的人格词汇区分为两种性别特征,以此来探讨自我概念长时记忆表征的性别化问题。实验设计为2(被试:男性与女性)×2(编码方式:自我参照编码与语义编码)×2(记忆项目类别:男性特征人格词汇与女性特征人格词汇)的混合因素设计。首先,实验结果进一步验证了自我参照效应的存在。其次,研究发现男性被试对于男性特征人格词汇的自我参照效应,显著高于女性特征人格词汇;女性被试的情况正好相反。实验结果表明,自我概念长时记忆表征系统对那些与自我性别相一致的人格特征词汇有比较好的组织编码形式,反映出自我对性别的认同。     

急性一氧化碳中毒高压氧治疗的中美指南比较

急性一氧化碳（carbonmonoxide,CO）中毒是中美最常见的意外中毒原因之一。高压氧能促进碳氧血红蛋白解离,加速体内CO排出,明显缩短CO半清除时间,是治疗急性CO中毒的一种重要治疗方法。比较中美现有急性CO中毒治疗指南及推荐意见。发现其中在高压氧治疗应用的适应证、具体方案、治疗费用等方面有很大差异。我们对此差异进行比较分析,为临床治疗及科研提供参考,也对通过进一步研究以充分证实高压氧治疗急性CO中毒的有效性,制订高压氧治疗最佳方案提出展望。     

Enhancement of the Post-training Cholinergic Tone Antagonizes the Impairment of Retention Induced by a Nitric Oxide Synthase Inhibitor in Mice

The present experiments examined the role of the central cholinergic system in the memory impairment induced by post-training administration of a nitric oxide synthase (NOS) inhibitor in mice. Male Swiss mice received a one-trial inhibitory avoidance training (0.8 mA, 50 Hz, 1-s footshock) followed immediately by an ip injection of the NOS inhibitor -N^G-nitroarginine methyl ester ( -NAME; 100 mg/kg). Retention (cut-off time, 300 s) was tested 48 h after training. The administration of -NAME results in memory impairment for the inhibitory avoidance task. The effects of -NAME (100 mg/kg, ip) on retention were reversed in a dose-related manner by the centrally acting anticholinesterase physostigmine (35, 70, or 150 μg/kg, sc) administered 30 min after the NOS inhibitor. Further, -NAME (100 mg/kg, ip)-induced memory impairment was completely antagonized by the centrally acting muscarinic cholinergic agonist oxotremorine (OTM; 25, 50, or 100 μg/kg, sc) when given 30 min after -NAME. The peripherally acting anticholinesterase neostigmine (150 μg/kg, sc) did not modify the memory-impairing effects of -NAME. These findings suggest that the memory impairment following post-training administration of a NOS inhibitor is mediated, at least in part, by a reduction of the activity of central muscarinic cholinergic mechanisms and are consistent with our previous view that nitric oxide may be involved in post-training neural processes underlying the storage of newly acquired information.     

On the Boundary: Family Therapy in a Long-Term Inpatient Setting

This paper presents a paradigm of family therapy in a long-term inpatient setting. After reviewing literature commenting on the necessity of attending to the needs of families of inpatients, the essential functions of inpatient treatment are discussed and an approach to family therapy, related to and reflecting those functions, is developed. Four functions of inpatient family therapy are delineated: joining, support, intervention, and validation. What distinguishes these from similar functions in outpatient treatment is the family therapist's position on the hospital-family boundary.     

Intracerebroventricular Infusion of the NMDA Receptor-Associated Glycine Site Antagonist 7-Chlorokynurenate Impairs Water Maze Performance but Fails to Block Hippocampal Long-Term Potentiation in Vivo

Most previous studies investigating the relationship betweenN-methyl- -aspartate receptor-dependent synaptic plasticity and learning have employed drugs that either compete with glutamate for access to the primary agonist binding site (e.g., -2-amino-5-phosphopentanoic acid) or block the associated ion channel (e.g., dizocilpine). This study targeted the glycine receptor site located on the NMDA receptor complex. Chronic intracerebroventricular infusion of the glycine site antagonist 7-chlorokynurenate (7CK; 75 mM, 0.5 μl/h, icv, for up to 14 days) impaired performance of male Lister hooded rats during acquisition of a spatial reference memory task in the water maze. In addition, however, these animals showed sensorimotor deficits, including a prolonged righting reflex, ataxia, and difficulty in staying on the escape platform. On completion of behavioral testing, the rats were anesthetized with urethane and an attempt was made to induce LTP in the hippocampus ipsilateral to the infusion cannula. Both control and 7CK-infused animals displayed equivalent long-term potentiation (LTP) 60 min posttetanus. A novel analytical technique for assaying drug tissue levels involving high-performance liquid chromotography with fluorescence detection revealed that tissue levels of 7CK in hippocampus were extremely low and unlikely to be sufficient to affect LTP, as observed. These findings neither support nor compromise the LTP/learning hypothesis, but they illustrate some of the problems of using drugs to elucidate the neurobiological mechanisms of learning and memory and the importance of a within-subjects design incorporating behavioral, physiological, and biochemical measures.