BACKGROUND & AIMS: Premotor respiratory neurons from neonatal rats express a Ba(2+)-insensitive outward rectifying K+ channel (KOR) which is activated by gamma-aminobutyric acid acting at its beta receptor. The biophysical properties of KOR are similar to those described for the S-channel (KS) which underlies simple forms of non-associative learning in the marine mollusc Aplysia. We show here that KOR, like the S-channel, is inhibited by cAMP. In addition, we demonstrate that this inhibition is due to a change in closed time kinetics. Our data suggests that the ionic and biochemical substrates underlying synaptic plasticity in Aplysia have been phylogenetically conserved in mammalian motor circuits such as that controlling rhythmic breathing movements.

背景与目标： 新生大鼠的运动前呼吸神经元表达Ba(2) 不敏感的向外整流K通道 (KOR)，该通道被作用于其 β 受体的 γ-氨基丁酸激活。KOR的生物物理性质与S通道 (KS) 所描述的相似，S通道 (KS) 是海洋软体动物中简单形式的非联想学习的基础。我们在这里展示了KOR，就像S通道一样，受到cAMP的抑制。此外，我们证明了这种抑制作用是由于封闭时间动力学的变化所致。我们的数据表明，Aplysia突触可塑性的离子和生化底物在哺乳动物运动回路 (例如控制有节奏的呼吸运动) 中已在系统发育中得到保守。

BACKGROUND & AIMS: :A morphologic study of the impact of aging on neuron marker expression was performed in different segments of the rat spinal cord. Spinal cord specimens from young (5 months), middle-aged (12 months) and senile (32 months) female rats were assessed. We found a complete loss of neuron-specific nuclear protein (NeuN) immunoreactivity in cervical, thoracic and lumbar segments of the senile animals whereas neuron-specific enolase (NSE) immunoreactivity was comparable in young and senile rats. These findings in otherwise morphologically well preserved spinal cord neurons are of interest and reveal that NeuN may not be a reliable marker to identify neurons in the spinal cord of aging rats.

背景与目标： : 在大鼠脊髓的不同节段中进行了衰老对神经元标志物表达影响的形态学研究。评估年轻 (5个月)，中年 (12个月) 和老年 (32个月) 雌性大鼠的脊髓标本。我们发现老年动物的颈，胸和腰段神经元特异性核蛋白 (NeuN) 免疫反应性完全丧失，而年轻和老年大鼠的神经元特异性烯醇化酶 (NSE) 免疫反应性相当。在其他形态学上保存良好的脊髓神经元中的这些发现令人感兴趣，并且表明NeuN可能不是鉴定衰老大鼠脊髓神经元的可靠标记。

BACKGROUND & AIMS: :When WGA-HRP (wheat germ agglutinin-horseradish peroxidase conjugate) was injected into the amygdala (lateral and basolateral amygdaloid nuclei) or entorhinal cortex of the cat, a number of nonpyramidal neurons in Ammon's horn were retrogradely labeled. The results indicate that some non-pyramidal neurons in Ammon's horn send projection fibers to the amygdala and entorhinal cortex.

背景与目标： : 将wga-hrp (小麦胚芽凝集素-辣根过氧化物酶缀合物) 注入猫的杏仁核 (外侧和基底外侧杏仁核) 或内嗅皮层时，将Ammon角中的许多非锥体神经元逆行标记。结果表明，Ammon角中的一些非锥体神经元向杏仁核和内嗅皮层发送投射纤维。

BACKGROUND & AIMS: :This study investigated the role of cellular antioxidant defense mechanisms in modulating the neurotoxicity of domoic acid (DomA), by using cerebellar granule neurons (CGNs) from mice lacking the modifier subunit of glutamate-cysteine ligase (Gclm). Glutamate-cysteine ligase (Glc) catalyzes the first and rate-limiting step in glutathione (GSH) biosynthesis. CGNs from Gclm (-/-) mice have very low levels of GSH and are 10-fold more sensitive to DomA-induced toxicity than CGNs from Gclm (+/+) mice. GSH ethyl ester decreased, whereas the Gcl inhibitor buthionine sulfoximine increased DomA toxicity. Antagonists of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptors and of N-methyl-D-aspartate (NMDA) receptors blocked DomA toxicity, and NMDA receptors were activated by DomA-induced l-glutamate release. The differential susceptibility of CGNs to DomA toxicity was not due to a differential expression of ionotropic glutamate receptors, as evidenced by similar calcium responses and L-glutamate release in the two genotypes. A calcium chelator and several antioxidants antagonized DomA-induced toxicity. DomA caused a rapid decrease in cellular GSH, which preceded toxicity, and the decrease was primarily due to DomA-induced GSH efflux. DomA also caused an increase in oxidative stress as indicated by increases in reactive oxygen species and lipid peroxidation, which was subsequent to GSH efflux. Astrocytes from both genotypes were resistant to DomA toxicity and presented a diminished calcium response to DomA and a lack of DomA-induced L-glutamate release. Because polymorphisms in the GCLM gene in humans are associated with low GSH levels, such individuals, as well as others with genetic conditions or environmental exposures that lead to GSH deficiency, may be more susceptible to DomA-induced neurotoxicity.

背景与目标： : 这项研究通过使用缺乏谷氨酸-半胱氨酸连接酶修饰亚基 (Gclm) 的小鼠的小脑颗粒神经元 (CGNs)，研究了细胞抗氧化防御机制在调节软骨藻酸 (DomA) 神经毒性中的作用。谷氨酸-半胱氨酸连接酶 (Glc) 催化谷胱甘肽 (GSH) 生物合成中的第一个和限速步骤。来自Gclm (-/-) 小鼠的CGNs的GSH水平非常低，并且对DomA诱导的毒性的敏感性比来自Gclm (/) 小鼠的CGNs高10倍。GSH乙酯降低，而Gcl抑制剂丁硫氨酸亚砜肟增加了DomA毒性。alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic/海藻酸盐受体和N-甲基-D-天冬氨酸 (NMDA) 受体的拮抗剂阻断了DomA毒性，并且NMDA受体被DomA诱导的l-谷氨酸释放激活。CGNs对DomA毒性的敏感性差异不是由于离子型谷氨酸受体的表达差异所致，这在两种基因型中钙反应和L-谷氨酸释放相似。钙螯合剂和几种抗氧化剂拮抗DomA诱导的毒性。DomA导致细胞GSH迅速下降，这先于毒性，并且下降主要是由于DomA诱导的GSH外排。DomA还引起了氧化应激的增加，如活性氧种类和脂质过氧化的增加所表明的，这是在GSH外排之后。两种基因型的星形胶质细胞均对DomA毒性具有抗性，并且对DomA的钙反应减弱，并且缺乏DomA诱导的L-谷氨酸释放。由于人类GCLM基因的多态性与低GSH水平相关，因此此类个体以及具有导致GSH缺乏的遗传条件或环境暴露的其他个体可能更容易受到DomA诱导的神经毒性的影响。

BACKGROUND & AIMS: Neural activity is thought to play a significant role during the development of the cerebral cortex. In this study, we examined the effects of global activity block or enhancement and the effects of patterned firing on the ability of cultured rat neocortical neurons to survive during the second week in vitro, beyond the beginning of synaptogenesis. Blockade of neuronal activity by adding tetrodotoxin (TTX) and increasing magnesium concentration in the medium strongly reduced the survival of cortical cells. Increasing neuronal activity by raising the external potassium concentration significantly improved the survival of cortical neurons. We postulated that in a developing neuronal network the survival of nerve cells is regulated by synaptically mediated events that involve changes in the intracellular calcium concentration. To examine this question further, we monitored the activity of the developing network by optically recording the intracellular calcium signals of many neurons simultaneously. These recordings show that in low magnesium neocortical neurons express synchronized oscillation of their intracellular calcium concentration. The ability of a network to synchronize the changes in intracellular calcium of multiple cells appeared gradually during the second week in culture, paralleled by both an increase in the synaptic density and a decline in the number of surviving neurons. By examining the fate of identified cells several days after a recording session, we found that those nerve cells that were co-activated with other neurons had a significantly higher chance to survive than cells that did not participate in synchronized events. These experiments demonstrate that during early cortical network development cortical neurons show synchronized firing activity and that the survival of neurons is at least partially dependent on this pattern of neuronal activity.

背景与目标： 神经活动被认为在大脑皮层发育过程中起着重要作用。在这项研究中，我们研究了整体活动阻滞或增强的影响以及图案化放电对培养的大鼠新皮层神经元在体外第二周 (突触开始后) 存活的能力的影响。通过添加河豚毒素 (TTX) 和增加培养基中的镁浓度来阻断神经元活性，从而大大降低了皮质细胞的存活。通过提高外部钾浓度来增加神经元活性，显着改善了皮质神经元的存活。我们推测，在发育中的神经元网络中，神经细胞的存活受到突触介导的事件的调节，这些事件涉及细胞内钙浓度的变化。为了进一步研究这个问题，我们通过同时光学记录许多神经元的细胞内钙信号来监测发育网络的活动。这些记录表明，在低镁的新皮层神经元中，其细胞内钙浓度表达同步振荡。在培养的第二周，网络使多个细胞的细胞内钙的变化同步的能力逐渐出现，同时突触密度增加和存活神经元数量减少。通过在记录过程几天后检查已识别细胞的命运，我们发现与其他神经元共同激活的神经细胞比不参与同步事件的细胞存活的机会要高得多。这些实验表明，在早期皮质网络发育过程中，皮质神经元显示出同步的放电活动，并且神经元的存活至少部分取决于这种神经元活动模式。

BACKGROUND & AIMS: :Medial preoptic area (MPOA) and ventral bed nucleus of the stria terminalis (VBST) neurons are involved in maternal behavior, but the neural sites to which the maternally relevant neurons project have not been determined. Since MPOA and VBST neurons express Fos during maternal behavior, we used a double-labeling immunocytochemical procedure to detect both Fos and a retrograde tracer, wheat germ agglutinin (WGA), in order to determine where these Fos neurons project. On Day 4 postpartum, fully maternal females were separated from their litters. On Day 5, WGA was iontophoretically injected into one of the following regions known to receive MPOA and/or VBST input: Lateral septum, medial hypothalamus at the level of the ventromedial nucleus, lateral habenula, ventral tegmental area, retrorubral field, or periaqueductal gray. On Day 7, females received a 2-h test with either pups or candy, after which they were perfused and their brains were processed for the detection of Fos and WGA. As expected, females tested with pups had more Fos-containing neurons in the MPOA and VBST than did females tested with candy. After WGA injections into several brain sites, the number of double-labeled cells observed in the MPOA and VBST was greater for the maternal females when compared to the non-maternal females. Therefore, these results pinpointed neural circuits that were activated during maternal behavior. For the maternal females, Fos-containing neurons in the MPOA projected most strongly to the medial hypothalamus at the level of the ventromedial nucleus and to the lateral septum, while Fos-containing neurons in the VBST projected most strongly to the retrorubral field, ventral tegmental area, and medial hypothalamus. Although relatively few MPOA and VBST neurons which expressed Fos during maternal behavior projected to the periaqueductal gray, these Fos-expressing neurons made up a relatively large proportion of the MPOA and VBST projection to the periaqueductal gray. This study suggests that MPOA and VBST efferents project to a variety of regions to promote full maternal responsiveness.

背景与目标： : 视前区 (MPOA) 和纹状体 (VBST) 神经元的腹床核参与母体行为，但尚未确定与母系相关的神经元投射到的神经部位。由于MPOA和VBST神经元在母体行为中表达Fos，因此我们使用双标记免疫细胞化学程序来检测Fos和逆行示踪剂小麦胚芽凝集素 (WGA)，以确定这些Fos神经元的投射位置。产后第4天，将完全的产妇与产仔分开。在第5天，将WGA离子电渗注射到以下已知接受MPOA和/或VBST输入的区域之一: 外侧隔膜，腹内侧核水平的下丘脑内侧，外侧habenula，腹侧被盖区，脑后野，或导水管周围灰色。在第7天，雌性接受了2小时的幼崽或糖果测试，然后对其进行灌注，并对其大脑进行处理以检测Fos和WGA。正如预期的那样，与用糖果测试的雌性相比，用幼崽测试的雌性在MPOA和VBST中具有更多的含Fos的神经元。在将WGA注射到多个大脑部位后，与非母体女性相比，在MPOA和VBST中观察到的双标记细胞数量更多。因此，这些结果确定了在母体行为期间激活的神经回路。对于母体女性，MPOA中含Fos的神经元最强烈地投射到腹内侧核水平的下丘脑内侧和外侧隔，而VBST中含Fos的神经元最强烈地投射到脑后野，腹侧被盖区和下丘脑内侧。尽管在投射到导水管周围灰色的母体行为中表达Fos的MPOA和VBST神经元相对较少，但这些表达Fos的神经元在MPOA和VBST投射到导水管周围灰色的比例相对较大。这项研究表明，MPOA和VBST传出剂投射到各个地区，以促进孕产妇的全面反应。

BACKGROUND & AIMS: :The effects of colorectal distension (CRD) were examined on neurons located in and around the nucleus submedius (Sm) in the medial thalamus of urethane-anesthetized rats. A total of 66 units (49 in the Sm and 17 in immediately surrounding regions) responding to cutaneous pinch were tested to examine their responsiveness to the CRD. All the neurons that responded to cutaneous stimulation were nociceptive specific (NS) neurons. Based on their responses to the CRD the Sm neurons were classified into three types as follows: 23 (47%) of 49 neurons in the Sm and three (18%) of 17 neurons near the Sm had tonic excitatory responses with long-lasting after-discharges (type I); nine (18%) Sm neurons and four (24%) peri-Sm neurons were tonically excited but had no after-discharge (type II); and seven (14%) Sm neurons were inhibited (type III). Ten (20%) Sm neurons and 10 (59%) peri-Sm neurons did not respond to CRD. All the excitatory and inhibitory responses to CRD increased with increasing CRD pressure. Simultaneous application of CRD and cutaneous pinch did not produce a reduced response (nocigenic inhibition). These results demonstrate that most of the Sm neurons receive convergent viscerosomatic inputs from the colon and/or rectum and from the skin, suggesting that the Sm may participate in visceral nociception.

背景与目标： : 检查了大肠扩张 (CRD) 对氨基甲酸乙酯麻醉大鼠内侧丘脑中中核 (Sm) 及其周围神经元的影响。测试了对皮肤挤压有反应的总共66个单位 (Sm中有49个，周围区域中有17个)，以检查它们对CRD的反应能力。所有对皮肤刺激有反应的神经元都是伤害性特异性 (NS) 神经元。根据对CRD的反应，Sm神经元分为三种类型: Sm中49个神经元中的23个 (47% 个) 和Sm附近的17个神经元中的3个 (18% 个) 具有强直兴奋反应，放电后持续时间长 (I型); 九个 (18%) Sm神经元和四个 (24%) 周围Sm神经元被音调兴奋，但没有放电后 (II型); 七个 (14%) Sm神经元被抑制 (III型)。10个 (20%) Sm神经元和10个 (59%) 周围Sm神经元对CRD没有反应。随着CRD压力的增加，对CRD的所有兴奋和抑制反应均增加。同时应用CRD和皮肤捏合不会产生降低的反应 (抑制)。这些结果表明，大多数Sm神经元从结肠和/或直肠以及皮肤接收会聚的内脏体输入，表明Sm可能参与内脏伤害感受。

BACKGROUND & AIMS: :Accumulating evidence indicates that Toll-like receptor (TLR) signaling adapter protein interactions with Toll/Interleukin-1 Receptor (TIR) domains present in sensory neurons may modulate neuropathic pain states. Following ligand interaction with TLRs, TIR serves to both initiate intracellular signaling and facilitate recruitment of signaling adapter proteins to the intracytoplasmic domain. Although TLR TIR is central to a number of TLR signaling cascades, its role in sensory neurons is poorly understood. In this study we investigated the degree to which TLR TIR decoy peptide modified to include a TAT sequence (Trans-Activator of Transcription gene in HIV; TAT-4BB) affected LPS-induced intracellular calcium flux and excitation in sensory neurons, and behavioral changes due to TLR4 active metabolite, morphine-3-glucuronide (M3G) exposure in vivo. TAT-4BB inhibited LPS-induced calcium changes in a majority of sensory neurons and decreased LPS-dependent neuronal excitability in small diameter neurons. Acute systemic administration of the TAT-4BB reversed M3G-induced tactile allodynia in a dose-dependent manner but did not affect motor activity, anxiety or responses to noxious thermal stimulus. These data suggest that targeting TLR TIR domains may provide novel pharmacological targets to reduce or reverse TLR4-dependent pain behavior in the rodent.

背景与目标： : 越来越多的证据表明，Toll样受体 (TLR) 信号衔接蛋白与感觉神经元中存在的Toll/Interleukin-1受体 (TIR) 结构域的相互作用可能调节神经性疼痛状态。配体与tlr相互作用后，TIR既可启动细胞内信号传导，又可促进信号衔接蛋白向胞浆内结构域的募集。尽管TLR TIR是许多TLR信号级联的核心，但对其在感觉神经元中的作用知之甚少。在这项研究中，我们调查了修饰为包含TAT序列 (HIV中转录基因的反式激活因子; TAT-4BB) 的TLR TIR诱饵肽对LPS诱导的细胞内钙通量和感觉神经元的兴奋以及由于TLR4活性代谢物引起的行为变化的影响程度，morphine-3-glucuronide (M3G) 体内暴露。TAT-4BB抑制了大多数感觉神经元中LPS诱导的钙变化，并降低了小直径神经元中LPS依赖性神经元的兴奋性。TAT-4BB的急性全身给药以剂量依赖性方式逆转了M3G-induced的触觉异常性疼痛，但不影响运动活动，焦虑或对有害热刺激的反应。这些数据表明，靶向TLR TIR结构域可以提供新的药理学靶标，以减少或逆转啮齿动物的TLR4-dependent疼痛行为。

BACKGROUND & AIMS: :The present study was designed to reveal the projection patterns of lateral hypothalamic (LH), cocaine- and amphetamine-regulated transcript (CART) neurons to the dorsal raphe (DR) and/or the locus coeruleus (LC) in the rat. After the injection of Red or Green Retrobeads into the DR or LC, LH sections were immunostained for CART and/or melanin-concentrating hormone (MCH). First, CART-immunoreactive axon terminals formed close appositions to the DR (or LC) neuronal profiles. Second, a subpopulation of CART neurons containing MCH projected to the monoaminergic nuclei; the majority of labeled neurons were observed in the dorsal hypothalamic area, the dorsal part of the posterior hypothalamic area, and the zona incerta. Cells were also observed in the perifornical part of the LH, the dorsomedial hypothalamic nucleus, the peduncular and the magnocellular parts of the LH. Of the total population of DR (or LC)-projecting cells, CART/MCH co-containing neurons were 9.5% ± 1.6% (or 10.8% ± 1.3% for LC). Finally, a subset of CART (or MCH) neurons provided divergent axon collaterals to the DR and the LC. Of the entire CART (or MCH) cell population, 3.9% ± 0.8% (or 5.6% ± 1.0% for MCH) sent axon collaterals to the DR/LC. CART/MCH co-containing neurons projecting to the DR or LC might be involved in the feeding-related regulation of arousal, stress-related responses, and emotional behaviors. Thus, CART (or MCH) cells that send divergent axon collaterals to the DR/LC might have a simultaneous (and possibly more efficient) way to exert their specific influences on the aminergic nuclei.

背景与目标： : 本研究旨在揭示下丘脑外侧 (LH)，可卡因和苯丙胺调节的转录本 (CART) 神经元向大鼠背侧中缝 (DR) 和/或蓝斑 (LC) 的投射模式。将红色或绿色的回珠注射到DR或LC中后，对LH切片进行了CART和/或黑色素浓缩激素 (MCH) 的免疫染色。首先，CART免疫反应性轴突末端与DR (或LC) 神经元谱形成紧密结合。其次，包含MCH的CART神经元亚群投射到单胺能核; 在下丘脑背侧区域，下丘脑后区域的背侧部分和透明带中观察到大多数标记的神经元。在LH的穹顶周围部分，下丘脑背核，LH的足部和大细胞部分也观察到细胞。在DR (或LC) 投射细胞的总数中，CART/MCH共含神经元为9.5% ± 1.6% (LC为10.8% ± 1.3%)。最后，CART (或MCH) 神经元的子集为DR和LC提供了不同的轴突侧支。在整个CART (或MCH) 细胞群中，3.9% ± 0.8% (或5.6% ± 1.0% MCH) 向DR/LC发送轴突侧支。向DR或LC投射的CART/MCH共含神经元可能参与了与喂养相关的唤醒调节，压力相关的反应和情绪行为。因此，向DR/LC发送不同轴突侧支的CART (或MCH) 细胞可能具有同时 (甚至可能更有效) 对氨基能核施加特定影响的方式。

BACKGROUND & AIMS: Paired helical filaments (PHFs) in the neurofibrillary tangles (NFTs) in Alzheimer's disease (AD) brains are composed of highly phosphorylated isoforms of tau (PHFtau) that fail to bind microtubules (MTs), and the levels of MT-binding competent tau are decreased in AD brains with abundant PHFtau. Because this loss of MT binding could compromise the viability of tangle-bearing AD neurons by destabilizing MTs, we asked whether these events could be initiated by inhibiting protein phosphatase 1 (PP1) and PP2A in cultured human neurons (NT2N cells) using okadaic acid (OK) and calyculin-A (CL-A). The treatment of NT2N cells with OK and CL-A increased tau phosphorylation, decreased the binding of tau to MTs, and selectively depolymerized the more stable detyrosinated MTs but not the more labile tyrosinated MTs. Significantly, this led to the rapid degeneration of axons, which are enriched in the more stable detyrosinated MTs, and PP2A was implicated in the initiation of this cascade of events because PP2A but not PP1 was closely associated with MTs in the NT2N cells. These studies imply that inactivation of PP2A in vulnerable neurons of the AD brain may play a mechanistic role in the conversion of normal tau into PHFtau, in the depolymerization of stable MTs, and in the degeneration of axons emanating from tangle-bearing neurons.

背景与目标： 阿尔茨海默氏病 (AD) 大脑的神经原纤维缠结 (nft) 中的成对螺旋细丝 (phf) 由高度磷酸化的tau亚型 (PHFtau) 组成，无法结合微管 (MTs)，并且MT结合的水平在具有丰富PHFtau的AD大脑中降低。因为MT结合的这种丧失可能会通过破坏MTs的稳定性而损害缠结AD神经元的生存能力，我们询问是否可以通过使用冈田酸 (OK) 和calyculin-A (cl-a) 抑制培养的人神经元 (NT2N细胞) 中的蛋白磷酸酶1 (PP1) 和PP2A来引发这些事件。用OK和CL-A处理NT2N细胞会增加tau的磷酸化，降低tau与MTs的结合，并选择性解聚更稳定的去酪氨酸化MTs，而不是更不稳定的酪氨酸化MTs。值得注意的是，这导致了轴突的快速变性，轴突在更稳定的去红细胞化MTs中富集，并且PP2A参与了该级联事件的启动，因为PP2A而不是PP1与NT2N细胞中的MTs密切相关。这些研究表明，AD大脑脆弱神经元中PP2A的失活可能在正常tau转化为PHFtau，稳定MTs的解聚以及缠结神经元产生的轴突变性中起机械作用。

BACKGROUND & AIMS: :Chronic stress in rats has been shown to impair learning and memory, and precipitate several affective disorders like depression and anxiety. The mechanisms involved in these stress-induced disorders and the possible reversal are poorly understood, thus limiting the number of drugs available for their treatment. Our earlier studies suggest cholinergic dysfunction as the underlying cause in the behavioral deficits following stress. Muscarinic cholinergic agonist, oxotremorine is demonstrated to have a beneficial effect in reversing brain injury-induced behavioral dysfunction. In this study, we have evaluated the effect of oxotremorine treatment on chronic restraint stress-induced cognitive deficits. Rats were subjected to restraint stress (6 h/day) for 21 days followed by oxotremorine treatment for 10 days. Spatial learning and memory was assessed in a partially baited eight-arm radial maze task. Stressed rats exhibited impairment in performance, with decreased percentage of correct choices and an increase in the number of reference memory errors (RMEs). Oxotremorine treatment (0.1 or 0.2 mg/kg, i.p.) to stressed rats resulted in a significant increase in the percent correct choices and a decrease in the number of RMEs compared with stress as well as the stress+vehicle-treated groups. In the retention test, oxotremorine treated rats committed less RMEs compared with the stress group. Chronic restraint stress decreased acetylcholinesterase (AChE) activity in the hippocampus, frontal cortex and septum, which was reversed by both the doses of oxotremorine. Further, oxotremorine treatment also restored the norepinephrine levels in the hippocampus and frontal cortex. Thus, this study demonstrates the potential of cholinergic muscarinic agonists and the involvement of both cholinergic and noradrenergic systems in the reversal of stress-induced learning and memory deficits.

背景与目标： : 大鼠的慢性压力已被证明会损害学习和记忆，并引发几种情感障碍，如抑郁和焦虑。对这些应激引起的疾病的机制和可能的逆转知之甚少，因此限制了可用于治疗的药物数量。我们早期的研究表明，胆碱能功能障碍是压力后行为缺陷的根本原因。毒蕈碱胆碱能激动剂氧代吗啡被证明在逆转脑损伤引起的行为功能障碍方面具有有益作用。在这项研究中，我们评估了氧代吗啡治疗对慢性束缚应激引起的认知缺陷的影响。对大鼠进行约束应激 (6 h/天) 21天，然后进行氧代雷丁治疗10天。在部分诱饵的八臂径向迷宫任务中评估了空间学习和记忆。应激大鼠的表现受损，正确选择的百分比降低，参考记忆错误 (rme) 的数量增加。与应激以及应激 + 媒介物处理组相比，对应激大鼠进行氧代雷丁处理 (0.1或0.2 mg/kg，i.p.) 导致正确选择百分比显着增加，rme数量减少。在保留试验中，与应激组相比，氧代雷莫林处理的大鼠产生的RMEs较少。慢性束缚应激降低了海马，额叶皮层和隔膜中的乙酰胆碱酯酶 (AChE) 活性，这两种剂量的氧代雷莫林都可以逆转。此外，氧代吗啡治疗还恢复了海马和额叶皮层中的去甲肾上腺素水平。因此，这项研究证明了胆碱能毒蕈碱激动剂的潜力，以及胆碱能和去甲肾上腺素能系统参与逆转应激诱导的学习和记忆缺陷。

BACKGROUND & AIMS: UNLABELLED:To identify the galanin-immunoreactive neurons projecting to the posterior lobe of the pituitary in the rat hypothalamus, a retrograde tracer (complex of wheat germ agglutinin-enzymatically inactive horseradish peroxidase-colloidal gold) was injected into the posterior lobe of the pituitary. Sections of the hypothalamus were treated with a combination of silver enhancement of retrogradely transported tracer and immunohistochemistry of galanin. Of the total number of hypothalamic cells doubly labeled with retrograde tracing and galanin-immunostaining, 56-60% were found in the supraoptic nucleus, 18-23% in the retrochiasmatic nucleus, 8-10% in the lateral magnocellular portion of the paraventricular nucleus. The ratio of (number of doubly labeled cells/number of galanin-immunoreactive cells) in each of the above regions was similar to the ratio of (number of retrogradely labeled cells/number of Nissl-stained cells) in the supraoptic nucleus. Of all retrogradely labeled cells in the hypothalamus, 51-56% also contained galaninlike immunoreactivity. IN CONCLUSION:(1) galanin-immunoreactive fibers in the posterior lobe of the pituitary originate mainly in the supraoptic nucleus, retrochiasmatic nucleus, and lateral magnocellular portion of the paraventricular nucleus, (2) most of galanin-immunoreactive cells in these regions project to the posterior lobe of the pituitary, and (3) about half the neurons constituting the hypothalamo-neurohypophyseal system contain galaninlike immunoreactivity.

背景与目标：

BACKGROUND & AIMS: Na(+)-Ca2+ exchanger-associated membrane currents were studied in cultured murine neocortical neurons, using whole-cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na+(o)-Ca2+(i)) exchange was evoked at -40 mV by switching external 140 mM Li+ to 140 mM Na+. The voltage dependence of this current was consistent with that predicted for 3Na+1Ca2+ exchange. As expected, the current depended on internal Ca2+, and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na+ from 3 to 20 mM or switching the external solution from 140 mM Li+ to 30 mM Na+ activated outward currents, consistent with reverse (Na+(i)-Ca2+(o)) exchange. An external Ca2(+)-sensitive current was also identified as associated with reverse Na(+)-Ca2+ exchange based on its internal Na+ dependence and sensitivity to XIP. Combined application of external Na+ and Ca2+ in the absence of internal Na+ triggered a 3.3-fold larger inward current than the current activated in the presence of 3 mM internal Na+, raising the intriguing possibility that Na(+)-Ca2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3-5 min of exposure to 100-200 microM glutamate, the forward exchanger current was significantly increased even when external Na+ was reduced to 100 mM, and the external Ca2(+)-activated reverse exchanger current was eliminated.

背景与目标： 使用全细胞记录结合细胞内灌注，在培养的鼠新皮层神经元中研究了Na ()-Ca2交换剂相关的膜电流。通过将外部140 mM Li切换到140 mM Na，在40 mV时诱发了与正向 (Na (o)-Ca2 (i)) 交换特别相关的净向内电流。该电流的电压依赖性与3Na 1Ca2交换的预测一致。如预期的那样，电流取决于内部Ca2，并且可以通过在细胞内应用交换抑制肽XIP来阻断电流。将内部Na + 从3升高到20 mm或将外部溶液从140 mM Li + 切换到30mm Na + 激活的外向电流，与反向 (Na +(i)-Ca2 +(o)) 交换一致。根据其内部Na依赖性和对XIP的敏感性，还确定了对外部Ca2 () 敏感的电流与反向Na ()-Ca2交换有关。在不存在内部Na的情况下组合施加外部Na和Ca2触发的内向电流比在3毫米内部Na存在下激活的电流大3.3倍，提出了Na ()-Ca2交换剂可能同时在正向和反向同时运行的有趣可能性，也许在不同的亚细胞位置。考虑到这一想法，我们研究了兴奋性谷氨酸受体激活对交换器操作的影响。暴露于100-200 microM谷氨酸3-5分钟后，即使外部Na降低到100 mM，正向交换电流也显着增加，并且消除了外部Ca2 () 激活的反向交换电流。

BACKGROUND & AIMS: :The projections of ventral medullary reticular neurons on both trigeminal (Vth) and hypoglossal (XIIth) motor nucleus were studied in sheep anesthetized with halothane. In a first series of experiments, extracellular microelectrodes were used to record the activity of medullary swallowing interneurons (SINs) located in the ventral region (around the nucleus ambiguus) of the swallowing center. Antidromic activation after electrical stimulation of the Vth and XIIth nuclei was tested in 83 SINs. For 38 SINs a clear antidromic activation was observed and for 8 of them the response was triggered by stimulation of either nucleus. As confirmed by the reciprocal collision test, these 8 SINs had branched axons sending information to both nuclei tested. Average latencies for antidromic activation of branched SINs after stimulation of the XIIth and the Vth motor nucleus were 2.2 +/- 0.6 ms and 2.7 +/- 0.8 ms respectively. The axonal conduction velocity of these neurons was 4.4 +/- 1.3 m/s for the collateral to the Vth motor nucleus and 2.7 +/- 0.7 m/s for axons projecting to the XIith motor nucleus. In a second series of experiments the double retrograde labeling technique was used to confirm the existence of neurons with branched axons in the medullary regions corresponding to the swallowing center. Small and well localized injections of Fast Blue (FB) and Diamidino Yellow (DY) fluorescent tracers were made in the Vth and in the XIIth motor nucleus respectively. A relatively large number of double-labeled cells was found in the ventral region of swallowing center (reticular formation around the nucleus ambiguus, 2-4 mm in front of obex).(ABSTRACT TRUNCATED AT 250 WORDS)

背景与目标： : 在氟烷麻醉的绵羊中研究了三叉神经 (Vth) 和舌下 (XIIth) 运动核上腹侧延髓网状神经元的投影。在第一系列实验中，细胞外微电极用于记录位于吞咽中心腹侧区域 (在核周围) 的髓质吞咽中间神经元 (SINs) 的活性。在83个SINs中测试了电刺激Vth和XIIth核后的反机器人激活。对于38个SINs，观察到明显的反机器人激活，其中8个是通过刺激任一核触发的。正如相互碰撞测试所证实的那样，这8个SINs具有分支的轴突，向两个测试的核发送信息。刺激XIIth和Vth运动核后，分支SINs的反抗激活的平均潜伏期分别为2.2/- 0.6 ms和2.7/- 0.8 ms。这些神经元的轴突传导速度对于Vth运动核的侧支为4.4/- 1.3 m/s，对于投射到XIith运动核的轴突为2.7/- 0.7 m/s。在第二系列实验中，使用双逆行标记技术来确认在对应于吞咽中心的髓质区域中存在具有分支轴突的神经元。分别在Vth和XIIth运动核中进行了快速蓝 (FB) 和二氨基黄 (DY) 荧光示踪剂的小且局部良好的注射。在吞咽中心的腹侧区域发现了相对大量的双标记细胞 (网状形成在核周围，在obex前面2-4毫米)。(摘要截短在250个单词)

BACKGROUND & AIMS: :Lycium barbarum polysaccharides (LBP) have been reported to have a wide range of beneficial effects including neuroprotection, anti-aging and anticancer. However, the anti-inflammation mechanism of LBP on primary cultured rat hippocampal neurons injured by oxygen-glucose deprivation/reperfusion (OGD/RP) is incompletely understood. We investigate the neuroprotective effects of LBP on neonatal rat primary cultured hippocampal neurons injured by OGD/RP with different approaches: MTT assay was used to detect cell viability, lactate dehydrogenase leakage was used to detect neuronal damage, formation of reactive oxygen species was determined by using fluorescent probe DCFH-DA. Hoechst 33,342 staining and TUNEL staining were used to determine the cell apoptosis. JC-1 was used to evaluate loss of mitochondrial membrane potential (MMP). The fluorescence intensity of [Ca2+]i in hippocampal neurons was determined by laser scanning confocal microscopy. The expression of various apoptotic markers such as TLR4, IκB, IL-6 and NF-κB were investigated by RT-PCR and western blot analysis. Results from each approach demonstrated that LBP increased the cell abilities and decreased the cell morphologic impairment. Furthermore, LBP increased MMP but inhibited [Ca2+]i elevation and significantly suppressed overexpression of NF-κB, IL-6 TLR4 and increased IκB expression.

背景与目标： : 据报道，枸杞多糖 (LBP) 具有广泛的有益作用，包括神经保护，抗衰老和抗癌。然而，LBP对氧-葡萄糖剥夺/再灌注 (OGD/RP) 损伤的原代培养大鼠海马神经元的抗炎机制尚不完全清楚。我们用不同的方法研究了LBP对OGD/RP损伤的新生大鼠原代培养海马神经元的神经保护作用: MTT法检测细胞活力，乳酸脱氢酶渗漏法检测神经元损伤，活性氧的形成通过荧光探针DCFH-DA。Hoechst 33,342染色和TUNEL染色用于确定细胞凋亡。JC-1用于评估线粒体膜电位 (MMP) 的丧失。用激光扫描共聚焦显微镜测定海马神经元 [Ca2] i的荧光强度。通过rt-pcr和western blot分析研究了各种凋亡标志物 (如TLR4，i κ b，IL-6和NF-κ b) 的表达。每种方法的结果均表明，LBP可提高细胞能力并减少细胞形态损伤。此外，LBP增加了MMP，但抑制了 [Ca2] i的升高，并显着抑制了NF-κ b的过表达，IL-6 TLR4和增加了i κ b的表达。