BACKGROUND & AIMS: :Glutamate (GLU) and gamma-amino butyric acid (GABA) are essential amino acids (AA) for brain function serving as excitatory and inhibitory neurotransmitter respectively. Their tablets are available in market for improving gut function and muscle performance. Despite of having a major role during memory formation and processing, effects of these tablets on brain functioning like learning and memory have not been investigated. Therefore, present study is aimed to investigate the effects of orally supplemented GLU and GABA on learning and memory performance and further to monitor related effects of these orally supplemented GLU and GABA on brain levels of these AA. Three groups of rats were supplemented orally with drinking water (control group) or suspension of tablets of GABA and Glutamate, respectively for four weeks. Cognitive performance was determined using behavioral tests (Novel object recognition test, Morris water maze, Passive avoidance test) measuring recognition, spatial reference and aversive memory. Levels of GLU, GABA and acetylcholine (ACh) were estimated in rat hippocampus. Results showed that chronic oral administration of GLU and GABA tablets has a significant impact on brain function and can alter GLU and GABA content in rat hippocampus. Compared to GABA, GLU supplementation specifically enhances memory performance via increasing ACh. Thus, GLU can be suggested as a useful supplement for improving learning and memory performance and neurochemical status of brain and in future could be effective in the treatment of neurological disorders affecting learning and memory performance.

背景与目标： ：谷氨酸（GLU）和γ-氨基丁酸（GABA）是大脑功能所必需的氨基酸（AA），分别充当兴奋性和抑制性神经递质。他们的片剂在市场上可用于改善肠道功能和肌肉性能。尽管在记忆形成和加工过程中起主要作用，但尚未研究这些片剂对大脑功能（如学习和记忆）的作用。因此，本研究旨在研究口服补充GLU和GABA对学习和记忆能力的影响，并进一步监测这些口服补充GLU和GABA对这些AA的脑水平的相关影响。向三组大鼠分别口服饮用水（对照组）或GABA和谷氨酸盐片剂的悬浮液，持续4周。使用行为测试（小说对象识别测试，莫里斯水迷宫，被动回避测试）来测量认知，空间参考和厌恶记忆，从而确定认知能力。估计大鼠海马中的GLU，GABA和乙酰胆碱（ACh）的水平。结果表明，长期口服GLU和GABA片剂对脑功能有显着影响，并且可以改变大鼠海马中GLU和GABA的含量。与GABA相比，GLU补充剂通过增加ACh来专门增强记忆力。因此，GLU可被建议作为改善学习和记忆性能以及大脑神经化学状态的有用补充剂，将来可能有效治疗影响学习和记忆性能的神经系统疾病。

BACKGROUND & AIMS: :A rapid elevation in the level of endogenous corticosterone (CORT) functions in the stress response associated with the hypothalamus-pituitary-adrenal axis, and it has been well documented that high levels of CORT play neurotoxic roles in the hippocampus. Both aging and the circadian rhythm possibly affect the sensitivity to CORT, although their endogenous modifications in the CORT-mediated events remain unclear. To explore the influence of age or circadian time on hippocampal vulnerability to excess CORT, we examined the relative mRNA expression of bcl-2 and bax in the dentate gyrus (DG) and the CA1 subfield, compared with the CA3 as an internal standard, after acute CORT administration using in situ RT-PCR. Male rats aged 10 weeks (young) or 6 months (adult) were treated with CORT at 0800 or 2000 h. The bcl-2 to bax mRNA ratio in the dentate gyrus (DG) was significantly decreased 2h after CORT exposure in the young rats treated at 0800 or 2000 h. In the adult rats, the treatment with CORT at 0800 h significantly decreased the bcl-2 to bax ratio, whereas the treatment at 2000 h was ineffective; the discrepancy between the treatment time points was apparent in adult rats, but not in young rats. Our results emphasize the importance of circadian time as well as age as a factor influencing the stress paradigm.

背景与目标： ：内源性皮质酮（CORT）水平的快速升高在下丘脑-垂体-肾上腺轴相关的应激反应中起作用，并且有充分的文献证明高水平的CORT在海马中发挥神经毒性作用。衰老和昼夜节律都可能影响对CORT的敏感性，尽管它们在CORT介导的事件中的内源性修饰尚不清楚。为了探讨年龄或昼夜节律时间对海马对过量CORT易损性的影响，我们比较了齿状回（DG）和CA1子域中bcl-2和bax的相对mRNA表达，并比较了CA3作为内标。使用原位RT-PCR进行急性CORT给药。将10周龄（年轻）或6个月龄（成年）的雄性大鼠在0800或2000 h进行CORT治疗。在0800或2000 h处理的年轻大鼠中，CORT暴露2h后，齿状回（DG）中bcl-2与bax mRNA的比例显着降低。在成年大鼠中，在0800 h用CORT处理可显着降低bcl-2与bax的比率，而在2000 h处理则无效。治疗时间点之间的差异在成年大鼠中很明显，而在年轻大鼠中则没有。我们的结果强调了昼夜节律的重要性以及年龄是影响压力范式的重要因素。

BACKGROUND & AIMS: OBJECTIVE:The effects of melatonin on antioxidant status were examined in pinealectomized rats using enzymatic, histological and immunohistochemical techniques. The aim of this study is to investigate the effects of melatonin on hippocampal apoptosis. MATERIALS AND METHODS:Male Wistar rats (n=21) were divided into 3 groups: Group I and group II were designated as control (sham-pinealectomy) and pinealectomized rats, respectively. Rats in group III were pinealectomized and injected daily with melatonin (1 mg/kg) for 3 months beginning at day 7 after surgery. At the end of experimental period, all rats were killed by decapitation. The brains of the rats were removed and the hippocampus tissue was obtained from all brain specimens. The right hippocampal specimens of all rats were used for determination of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and malondialdehyde (MDA) levels. The left hippocampus tissue specimens of all animals were used for immunohistochemical and histological evaluation. RESULTS:The levels of SOD and GSH-Px were significantly decreased, and MDA levels were significantly increased in pinealectomized rats compared to the controls. In the histological and immunohistochemical evaluation of this group, increase of pyknotic cells, vacuolar degeneration and apoptosis were observed. However, increased SOD and GSH-Px enzyme activities, and decreased MDA levels were detected in the rats administered melatonin after pinealectomy. Furthermore, histological and apoptotic changes in hippocampus caused by pinealectomy were lost in the rats treated with melatonin. CONCLUSIONS:The results of our study revealed that pinealectomy-induced oxidative damage and morphological changes in the hippocampal tissue were suppressed by melatonin.

背景与目标： 目的：采用酶法，组织学和免疫组化技术研究褪黑激素对松果体切除大鼠的抗氧化状态的影响。这项研究的目的是研究褪黑激素对海马细胞凋亡的影响。
材料与方法：雄性Wistar大鼠（n = 21）分为3组：将I组和II组分别作为对照组（假松果体切除术）和松果体切除的大鼠。从手术后第7天开始，对第三组的大鼠进行松果体切除术，并每天注射褪黑激素（1 mg / kg），持续3个月。在实验期结束时，所有大鼠被斩首处死。取出大鼠的大脑，并从所有脑标本中获得海马组织。所有大鼠的右海马标本用于测定超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GSH-Px）和丙二醛（MDA）水平。所有动物的左海马组织标本用于免疫组织化学和组织学评估。
结果：与对照组相比，松果体切除的大鼠的SOD和GSH-Px水平显着降低，MDA水平显着升高。在该组的组织学和免疫组织化学评价中，观察到了泌尿生殖细胞的增加，液泡变性和细胞凋亡。然而，在松果体切除术后施用褪黑激素的大鼠中检测到SOD和GSH-Px酶活性增加，而MDA水平降低。此外，褪黑素治疗的大鼠失去了由松果体切除术引起的海马组织学和凋亡的改变。
结论：我们的研究结果表明，褪黑素能抑制松果体切除术引起的海马组织氧化损伤和形态变化。

BACKGROUND & AIMS: :Diabetes mellitus (DM) may give rise to cognitive impairment, but the pathological mechanism involved was still unknown. We employed streptozotocin (STZ)-induced diabetic rats and test their capacity for learning and memory by three-arm radial maze. We determined the expression level of growth-associated protein-43 (GAP-43) and mitogen activated protein kinase phosphatase-1 (MKP-1) in the hippocampus by immunohistochemistry. MKP-1 mRNA level in the CA1 and dentate gyrus (DG) Hippocampal area is further determined by RT-PCR method. We also observed the ultrastructures of Hippocampal neurons by transmission electron microscopy (TEM). All data were analyzed by the independent samples t-test. Four weeks after STZ induction, the diabetic rats showed decreased capacity for learning and memory as indicated by the increase in the error number and reaction time in three-arm radial maze test. TEM results showed the ultrastructures of diabetic hippocampus, including area CA1 and DG, neurons were characterized by swollen mitochondria, increased heterochromatin accumulation and reduced synaptic contacts. The optical density as well as the positive neuron number for GAP-43 and MKP-1 decreased significantly in the CA1 and DG Hippocampal area in diabetic rats (P<0.01). RT-PCR results also showed MKP-1 mRNA in the CA1 and DG Hippocampal area was decreased in the diabetic rats. These results indicated that DM could down-regulate GAP-43 and MKP-1 expression in Hippocampal area that is in charge of memory and cognition. As indicated by our study, the changes in GAP-43 and MKP-1 expression in hippocampus may play a role in the pathogenesis of diabetic dementia.

背景与目标： ：糖尿病（DM）可能引起认知障碍，但涉及的病理机制仍不清楚。我们采用了链脲佐菌素（STZ）诱导的糖尿病大鼠，并通过三臂radial骨迷宫测试了它们的学习和记忆能力。我们通过免疫组织化学测定了海马中的生长相关蛋白43（GAP-43）和有丝分裂原活化蛋白激酶磷酸酶1（MKP-1）的表达水平。通过RT-PCR方法进一步测定CA1和齿状回（DG）海马区中的MKP-1 mRNA水平。我们还通过透射电子显微镜（TEM）观察了海马神经元的超微结构。所有数据均通过独立样本t检验进行分析。诱导STZ后四周，糖尿病大鼠的学习和记忆能力下降，这是通过三臂放射状迷宫测试中错误数和反应时间的增加来表明的。 TEM结果显示，糖尿病海马的超微结构包括CA1区和DG区，神经元的特征在于线粒体肿胀，异染色质积累增加和突触接触减少。糖尿病大鼠CA1区和DG海马区的GAP-43和MKP-1的光密度以及阳性神经元数量均显着下降（P <0.01）。 RT-PCR结果还显示，糖尿病大鼠CA1和DG海马区的MKP-1 mRNA降低。这些结果表明DM可以下调负责记忆和认知的海马区GAP-43和MKP-1的表达。正如我们的研究所表明的，海马区GAP-43和MKP-1表达的变化可能在糖尿病性痴呆的发病机理中起作用。

BACKGROUND & AIMS: :Intermittent hypoxia, such as that associated with obstructive sleep apnea, can cause neuronal death and neurobehavioral dysfunction. The cellular and molecular mechanisms through which hypoxia alter hippocampal function are incompletely understood. This study used in vitro [(35)S]guanylyl-5'-O-(gamma-thio)-triphosphate ([(35)S]GTP gamma S) autoradiography to test the hypothesis that carbachol and DAMGO activate hippocampal G proteins. In addition, this study tested the hypothesis that in vivo exposure to different oxygen (O(2)) concentrations causes a differential activation of G proteins in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus. G protein activation was quantified as nCi/g tissue in CA1, CA3, and DG from rats housed for 14 days under one of three different oxygen conditions: normoxic (21% O(2)) room air, or hypoxia (10% O(2)) that was intermittent or sustained. Across all regions of the hippocampus, activation of G proteins by the cholinergic agonist carbachol and the mu opioid agonist [D-Ala(2), N-Met-Phe(4), Gly(5)] enkephalin (DAMGO) was ordered by the degree of hypoxia such that sustained hypoxia > intermittent hypoxia > room air. Carbachol increased G protein activation during sustained hypoxia (38%), intermittent hypoxia (29%), and room air (27%). DAMGO also activated G proteins during sustained hypoxia (52%), intermittent hypoxia (48%), and room air (43%). Region-specific comparisons of G protein activation revealed that the DG showed significantly less activation by carbachol following intermittent hypoxia and sustained hypoxia than the CA1. Considered together, the results suggest the potential for hypoxia to alter hippocampal function by blunting the cholinergic activation of G proteins within the DG.

背景与目标： ：间歇性缺氧，例如与阻塞性睡眠呼吸暂停有关的缺氧，可能导致神经元死亡和神经行为功能障碍。缺氧改变海马功能的细胞和分子机制尚不完全清楚。这项研究使用体外[（35）S]胍基-5'-O-（γ-硫代）-三磷酸（[（35）S] GTPγS）放射自显影，以检验卡巴胆碱和DAMGO激活海马G蛋白的假说。此外，这项研究检验了以下假设：体内暴露于不同的氧气（O（2））浓度会导致海马CA1，CA3和齿状回（DG）区域中G蛋白的差异激活。 G蛋白活化被量化为在以下三种不同氧气条件之一下饲养14天的大鼠在CA1，CA3和DG中的nCi / g组织：常氧（21％O（2））室内空气或低氧（10％O（ 2））是断断续续的或持续的。在海马的所有区域，胆碱能激动剂卡巴胆碱和μ阿片类激动剂[D-Ala（2），N-Met-Phe（4），Gly（5）]脑啡肽（DAMGO）激活G蛋白的顺序是：缺氧程度，使持续缺氧>间歇性缺氧>室内空气。在持续缺氧（38％），间歇性缺氧（29％）和室内空气（27％）期间，卡巴胆碱会增加G蛋白的活化。 DAMGO还可以在持续性缺氧（52％），间歇性缺氧（48％）和室内空气（43％）期间激活G蛋白。 G蛋白活化的区域特异性比较显示，间歇性缺氧和持续性缺氧后DG所显示的DG活化程度明显低于CA1。综合考虑，结果表明缺氧可能通过减弱DG中G蛋白的胆碱能激活来改变海马功能。

BACKGROUND & AIMS: :Dendrotoxins, important pharmacological tools for studying K(+) channels, are potently convulsant in the central nervous system and evidence suggests that different members of the dendrotoxin family may act at pre- or post-synaptic sites. Using a combination of intrahippocampal infusion, microdialysis and electroencephalograph (EEG) recording, we have compared the effects of alpha-dendrotoxin and dendrotoxin K on extracellular levels of excitatory amino acids in anaesthetised rats. Our findings show that although infusion of 35 pmol of both peptides was associated with elevated extracellular aspartate and glutamate, these increased levels were more sustained with dendrotoxin K. Furthermore, there was EEG evidence of an associated transient functional change consistent with an action on pre-synaptic K(+) channels. In contrast, infusion of alpha-dendrotoxin produced only a brief effect on amino acid levels and no evidence of a functional consequence.

背景与目标： ：Dendrotoxins是研究K（）通道的重要药理工具，在中枢神经系统中很强惊厥，证据表明树突毒素家族的不同成员可能在突触前或突触后部位起作用。使用海马内输注，微透析和脑电图（EEG）记录的组合，我们比较了α-树突毒素和树突毒素K对麻醉大鼠兴奋性氨基酸细胞外水平的影响。我们的发现表明，尽管输注35 pmol的两种肽都与升高的细胞外天冬氨酸和谷氨酸有关，但树突毒素K可使这些升高的水平更持久。突触K（）通道。相反，输注α-树突毒素仅对氨基酸水平产生短暂影响，而没有功能后果的证据。

BACKGROUND & AIMS: :The 5-hydroxytryptamine (5-HT; serotonin) transporter (5-HTT) is important in terminating serotonergic neurotransmission and is a primary target for many psychotherapeutic drugs. Study of the regulation of 5-HTT activity is therefore important in understanding the control of serotonergic neurotransmission. Using high-speed chronoamperometry, we have demonstrated that local application of 5-HT(1B) antagonists into the CA3 region of the hippocampus prolongs the clearance of 5-HT from extracellular fluid (ECF). In the present study, we demonstrate that the 5-HT(1B) antagonist cyanopindolol does not produce this effect by increasing release of endogenous 5-HT or by directly binding to the 5-HTT. Dose-response studies showed that the potency of cyanopindolol to inhibit clearance of 5-HT was equivalent to that of the selective 5-HT reuptake inhibitor fluvoxamine. Local application of the 5-HT(1A) antagonist WAY 100635 did not alter 5-HT clearance, suggesting that the effect of cyanopindolol to prolong clearance is not via a mechanism involving 5-HT(1A) receptors. Finally, the effect of low doses of cyanopindolol and fluvoxamine to inhibit clearance of 5-HT from ECF was additive. These data are consistent with the hypothesis that activation of terminal 5-HT(1B) autoreceptors increases 5-HTT activity.

背景与目标： ：5-羟色胺（5-HT; 5-羟色胺）转运蛋白（5-HTT）在终止5-羟色胺能神经传递中很重要，并且是许多心理治疗药物的主要靶标。因此，研究5-HTT活性的调节对理解5-羟色胺能神经传递的控制是重要的。使用高速计时电流分析法，我们已经证明将5-HT（1B）拮抗剂局部应用到海马CA3区可以延长5-HT从细胞外液（ECF）的清除。在本研究中，我们证明了5-HT（1B）拮抗剂氰基吲哚洛尔不会通过增加内源性5-HT的释放或直接与5-HTT结合而产生这种作用。剂量反应研究表明，氰基吲哚醇抑制5-HT清除的效力与选择性5-HT再摄取抑制剂氟伏沙明的效力相当。 5-HT（1A）拮抗剂WAY 100635的局部应用不会改变5-HT的清除率，这表明氰基吲哚洛尔延长清除率的作用不是通过涉及5-HT（1A）受体的机制进行的。最后，低剂量的氰基吲哚洛尔和氟伏沙明抑制5-HT从ECF清除的作用是加和的。这些数据与终端5-HT（1B）自身受体激活增加5-HTT活性的假设是一致的。

BACKGROUND & AIMS: :The dentate gyrus of the hippocampus continues generating new neurons throughout life. These neurons originate from radial astrocytes within the subgranular zone (SGZ). Here, we find that Sox1, a member of the SoxB1 family of transcription factors, is expressed in a subset of radial astrocytes. Lineage tracing using Sox1-tTA;tetO-Cre;Rosa26 reporter mice shows that the Sox1-expressing cells represent an activated neural stem/progenitor population that gives rise to most if not all newly born granular neurons, as well as a small number of mature hilar astrocytes. Furthermore, a subpopulation of Sox1-marked cells have long-term neurogenic potential, producing new neurons 3 months after inactivation of tetracycline transactivator. Remarkably, after 8 weeks of labeling and a 12-week chase, as much as 44% of all granular neurons in the dentate gyrus were derived from Sox1 lineage-traced adult neural stem/progenitor cells. The fraction of Sox1-positive cells within the radial astrocyte population decreases with age, correlating with a decrease in neurogenesis. However, expression profiling shows that these cells are transcriptionally stable throughout the lifespan of the mouse. These results demonstrate that Sox1 is expressed in an activated stem/progenitor population whose numbers decrease with age while maintaining a stable molecular program.

背景与目标： 海马的齿状回在整个生命中继续产生新的神经元。这些神经元起源于颗粒下带（SGZ）内的星形星形胶质细胞。在这里，我们发现Sox1，SoxB1家族的转录因子家族的成员，在radial状星形胶质细胞的子集中表达。使用Sox1-tTA; tetO-Cre; Rosa26报告基因小鼠的谱系追踪显示，表达Sox1的细胞代表一个激活的神经干/祖细胞群，该群体会产生大多数（如果不是全部）新生的颗粒神经元，以及少数成熟的神经元。肺门星形胶质细胞。此外，Sox1标记的细胞亚群具有长期的神经源性潜力，在灭活四环素反式激活剂后3个月会产生新的神经元。值得注意的是，标记8周和追踪12周后，齿状回中多达44％的所有颗粒神经元均来自Sox1谱系追踪的成年神经干/祖细胞。星形星形胶质细胞群中Sox1阳性细胞的比例随年龄的增长而降低，这与神经发生的减少有关。但是，表达谱显示这些细胞在小鼠的整个生命周期中都是转录稳定的。这些结果表明，Sox1在活化的茎/祖细胞中表达，其数量随着年龄的增长而减少，同时保持稳定的分子程序。

BACKGROUND & AIMS: Hippocampal GABAergic interneurons are responsible for controlling the output and efficacy of synaptic input of large principal cell populations and, thereby, determine the oscillatory discharge patterns and synaptic plasticity in the hippocampus. Single interneurons are able to prevent repetitive firing of postsynaptic pyramidal cells (R. Miles, K. Tóth, A.I. Gulyás, N. Hájos, and T.F. Freund. Neuron, 16815-823, 1996), whereas on occasion a single pyramidal cell may be able to activate an interneuron under in vitro conditions (A.I. Gulyás, R. Miles, A. Sik, K. Tóth, N. Tamamaki, and T.F. Freund.

Nature (London), 366683-687, 1993). Inhibition is therefore extremely powerful. Transient suppression of interneuronal activity allows the precise timing and synchronization of inhibitory postsynaptic potentials arriving at principal cells.

A rhythmic suppression or modulation of interneuron discharge may be brought about by input from at least two major sources(i) from other local interneurons or (ii) from subcortical centers. Of the possible local sources, in the present review particular attention will be paid to GABAergic neurons specialized to innervate other interneurons. Subcortical pathways known to modulate specific inhibitory functions in the hippocampus, i.e., the GABAergic and cholinergic septohippocampal and the serotonergic raphe hippocampal pathways, will also be reviewed. Roles of these control mechanisms may include the generation of theta and higher frequency oscillations and the selective removal of inhibition from the termination zone of specific excitatory afferents, thereby increasing their efficacy and (or) plasticity.

背景与目标： 海马GABA能性神经元负责控制大量主细胞群的输出和突触输入的功效，从而确定海马中的振荡放电模式和突触可塑性。单个中间神经元能够阻止突触后锥体细胞的反复发射（R. Miles，K.Tóth，AIGulyás，N.Hájos和TF Freund。Neuron，16815-823，1996），而有时单个锥体细胞可能是能够在体外条件下激活中间神经元（AIGulyás，R.Miles，A.Sik，K.Toth，N.Tamamaki和TF Freund。

Nature（London），366683-687，1993） 。因此抑制作用非常强大。神经元间活动的瞬时抑制可以使到达主细胞的抑制性突触后电位的精确定时和同步。

至少从两个主要来源（i）的输入可以实现对神经元放电的节律性抑制或调节。其他局部中间神经元；或（ii）来自皮层下中心。在可能的本地来源中，在本综述中，将特别关注专门用于支配其他中间神经元的GABA能神经元。也将审查已知可调节海马中特定抑制功能的皮层下途径，即GABA能和胆碱能的海马途径和血清素能的罗非鱼海马途径。这些控制机制的作用可能包括产生theta和更高频率的振荡，以及选择性地消除特定兴奋性传入传入末端区域的抑制作用，从而提高其功效和（或）可塑性。

BACKGROUND & AIMS: Previously, we demonstrated that transection of the fimbria/fornix blocked the excitatory effect of corticotropin-releasing hormone (CRH) on startle (CRH-enhanced startle), suggesting that the hippocampus and its efferent target areas that communicate via the fimbria may be critically involved in CRH-enhanced startle. The bed nucleus of the stria terminalis (BNST) receives direct projections from the ventral hippocampus via the fimbria/fornix. Therefore, the role of the ventral hippocampus, the BNST, and the amygdala in CRH-enhanced startle was investigated. NMDA lesions of the BNST completely blocked CRH-enhanced startle, whereas chemical lesions of the ventral hippocampus and the amygdala failed to block CRH-enhanced startle. However, the same amygdala-lesioned animals showed a complete blockade of fear-potentiated startle, a conditioned fear response sensitive to manipulations of the amygdala. In contrast, BNST-lesioned rats had normal fear-potentiated startle. This indicates a double dissociation between the BNST and the amygdala in two different paradigms that enhance startle amplitude. Microinfusions of CRH into the BNST, but not into the ventral hippocampus, mimicked intracerebroventricular CRH effects. Furthermore, infusion of a CRH antagonist into the BNST blocked CRH-enhanced startle in a dose-dependent manner. Control studies showed that this blockade did not result from either leakage of the antagonist into the ventricular system or a local anesthetic effect caused by infusion of the antagonist into the BNST. The present studies strongly suggest that CRH in the CSF can activate the BNST, which could lead to activation of brainstem and hypothalamic BNST target areas involved in anxiety and stress responses.

背景与目标： 先前，我们证明了横隔纤维/穹ni横断阻止了促肾上腺皮质激素释放激素（CRH）对惊吓（CRH增强的惊吓）的兴奋作用，这表明海马及其通过突触进行沟通的目标区域可能受到了严重影响。令CRH惊呆了。末端纹状体的床核（BNST）通过腹膜/穹receives从腹侧海马接受直接投射。因此，研究了腹侧海马，BNST和杏仁核在CRH增强惊吓中的作用。 BNST的NMDA损伤完全阻断了CRH增强的惊吓，而腹侧海马和杏仁核的化学损伤未能阻断CRH增强的惊吓。然而，相同的扁桃体病变动物表现出对恐惧增强惊吓的完全阻断，这是一种对杏仁核的操纵敏感的条件化恐惧反应。相反，BNST损伤的大鼠具有正常的恐惧增强惊吓。这表明BNST和杏仁核之间在两种不同的范式之间双重解离，从而增强了惊吓幅度。将CRH微量注入BNST，但不注入腹侧海马区，模仿了脑室内CRH效应。此外，将CRH拮抗剂输注到BNST中以剂量依赖的方式阻断了CRH增强的惊吓。对照研究表明，这种阻断作用不是由拮抗剂渗入心室系统引起的，也不是由将拮抗剂注入BNST引起的局部麻醉作用引起的。本研究强烈表明，CSF中的CRH可以激活BNST，这可能导致涉及焦虑和压力反应的脑干和下丘脑BNST目标区域激活。

BACKGROUND & AIMS: :The neonatal hippocampus exhibits regularly recurring waves of synchronized neuronal activity in vitro. Because active sleep (AS), characterized by bursts of phasic motor activity in the form of myoclonic twitching, may provide conditions that are conducive to activity-dependent development of hippocampal circuits, we hypothesized that the waves of synchronous neuronal activity that have been observed in vitro would be associated with AS-related twitching. Using unanesthetized 1- to 12-d-old rats, we report here that the majority of neurons in CA1 and the dentate gyrus (DG) are significantly more active during AS than during either quiet sleep or wakefulness. Neuronal activity typically occurs in phasic bursts, during which most neurons are significantly cross-correlated both within and across the CA1 and DG fields. All AS-active neurons increase their firing rates during periods of myoclonic twitching of the limbs, and a subset of these neurons exhibit a burst of activity immediately after limb twitches, suggesting that the twitches themselves provide sensory feedback to the infant hippocampus, as occurs in the infant spinal cord and neocortex. Finally, the synchronous bursts of neuronal activity are coupled to the emergence of the AS-related hippocampal gamma rhythm during the first postnatal week, as well as the emergence of the AS-related theta rhythm during the second postnatal week. We hypothesize that the phasic motor events of active sleep provide the developing hippocampus with discrete sensory stimulation that contributes to the development and refinement of hippocampal circuits as well as the development of synchronized interactions between hippocampus and neocortex.

背景与目标： ：新生的海马体在体外表现出定期重复出现的同步神经元活动。由于活动性睡眠（AS）以肌阵挛性抽搐形式的阶段性运动活动爆发为特征，可能提供有利于活动依赖型海马回路发展的条件，因此我们假设已观察到同步神经元活动波体外会与AS相关的抽搐有关。使用未麻醉的1至12天大的大鼠，我们在此报告，在AS期间，CA1和齿状回（DG）中的大多数神经元比安静睡眠或清醒期间的神经元活跃得多。神经元活动通常发生在阶段性爆发中，在此期间，大多数神经元在CA1和DG场内和跨CA1和DG场都具有显着的互相关性。在四肢肌阵挛性抽搐期间，所有AS活跃神经元均会提高放电率，这些神经元的一部分在四肢抽搐后立即表现出爆发性活动，这表明抽搐本身会向婴儿海马提供感觉反馈，就像在四肢抽搐时一样。婴儿脊髓和新皮层。最后，神经元活动的同步爆发与产后第一周出现AS相关的海马γ节奏，以及产后第二周出现AS相关theta节奏有关。我们假设主动睡眠的阶段性运动事件为发展中的海马提供了离散的感觉刺激，从而促进了海马电路的发展和完善以及海马与新皮层之间同步相互作用的发展。

BACKGROUND & AIMS: :Post-traumatic stress disorder (PTSD) is characterized by memory disturbances following trauma. Acute predator threat has emerged as an ethological model of PTSD, yet the effects of predator odor on signaling cascades associated with long-term memory remain poorly understood. In this study, we exposed male and female Wistar rats to the synthetic predator odor 2,5-dihydro-2,4,5-trimethylthiazoline (TMT) to assess behavioral and physiological responses as well as rapid modulation of signal transduction cascades associated with learning and memory in the male and female hippocampus. During exposure to TMT in the homecage, both male and female animals displayed robust immobility, avoidance, and altered activity as a function of time. Physiologically, TMT exposure increased circulating corticosterone and blood glucose in both male and female rodents, suggesting that TMT evokes sex-independent behavioral and physiological responses. With respect to signal transduction, TMT exposure rapidly reduced phosphorylation of cyclic-adenosine monophosphate response element binding protein (CREB) in the male, but not the female hippocampus. Furthermore, TMT exposure reduced phosphorylation of extracellular signal-regulated kinase 1/2 and increased nuclear expression of the synapto-nuclear messenger protein Jacob in the male hippocampus, consistent with activation of the CREB shut-off pathway. In a follow-up behavioral experiment, post-training exposure to TMT did not affect spatial water maze performance of male rats. However, male rats re-introduced to the context in which TMT had previously been presented displayed avoidance and hyperactivity, but not freezing behavior or elevated corticosterone responses, suggesting that TMT exposure supports a form of contextual conditioning which is not characterized by immobility. Taken together, our findings suggest that TMT evokes similar behavioral and physiological responses in male and female Wistar rats, but affects distinct signaling cascades in the male and female hippocampus which may contribute to behavioral disruptions associated with predator exposure.

背景与目标： 创伤后应激障碍（PTSD）的特征是创伤后的记忆障碍。急性捕食者威胁已成为PTSD的一种行为学模型，但对捕食者气味对与长期记忆相关的信号级联反应的影响仍知之甚少。在这项研究中，我们将雄性和雌性Wistar大鼠暴露于合成的捕食性气味2,5-二氢-2,4,5-三甲基噻唑啉（TMT）中，以评估行为和生理反应以及与学习相关的信号转导级联的快速调节和雌性海马的记忆。在笼子中暴露于TMT期间，雄性和雌性动物均表现出强健的不动，回避和随时间变化的活动。从生理上讲，TMT暴露会增加雄性和雌性啮齿动物的循环皮质酮和血糖，这表明TMT引起了与性别无关的行为和生理反应。关于信号转导，TMT暴露可迅速减少雄性海马中环磷酸腺苷单磷酸反应元件结合蛋白（CREB）的磷酸化。此外，TMT暴露减少了雄性海马中细胞外信号调节激酶1/2的磷酸化并增加了突触核信使蛋白Jacob的核表达，这与CREB阻断途径的激活相一致。在一项后续的行为实验中，训练后暴露于TMT并没有影响雄性大鼠的空间水迷宫性能。然而，重新引入先前曾提出过TMT的情境的雄性大鼠表现出回避和过度活跃，但没有冰冻行为或皮质酮反应升高，这表明TMT暴露支持一种形式的情境调节，其特征是不动。两者合计，我们的发现表明TMT在雄性和雌性Wistar大鼠中引起相似的行为和生理反应，但会影响雄性和雌性海马中不同的信号传导级联，这可能导致与捕食者接触相关的行为破坏。

BACKGROUND & AIMS: BACKGROUND:Hippocampal functions are sensitive to sleep deficiency. Dopamine D1 receptor (D1R) in hippocampus can regulate the expression of cAMP response element binding protein (CREB) through PKA, MAPK and phosphoinositide pathway, but which pathway plays the major role in hippocampus during Chronic sleep deprivation (CSD) is unclear. METHODS:The CSD model was created, SKF rats were administered the D1R agonist (SKF38363), and hippocampus from each animal was dissected for following molecular detection. The gene and protein levels of CREB and key molecules in D1R pathways were measured by real-time PCR and western blotting, respectively. RESULTS:Both the gene and protein expression of CREB in hippocampus decreased by CSD and improved significantly by SKF38393 (p<0.05). Both the gene and protein expression of PKA in hippocampus decreased by CSD and improved significantly by SKF38393 (p<0.05). SKF38393 just significantly improved the gene level of CaMK IV and the protein level of p-CaMK IV (p<0.05) in CSD rats, but it cannot improve the protein expression of ERK1/2 and p-ERK1/2. DISCUSSION:CSD significantly decreased the expression of CREB in hippocampus. As the key molecules, PKA and CaMK IV play an important role during the improvement of hippocampus by the activation of D1R, and this process might be improved during CSD through the PKA and phosphoinositide pathway.

背景与目标： 背景：海马功能对睡眠不足敏感。海马中的多巴胺D1受体（D1R）可以通过PKA，MAPK和磷酸肌醇途径调节cAMP反应元件结合蛋白（CREB）的表达，但是在慢性睡眠剥夺（CSD）期间，该途径在海马中起主要作用尚不清楚。
方法：建立CSD模型，给SKF大鼠施用D1R激动剂（SKF38363），并解剖每只动物的海马体以进行分子检测。通过实时PCR和蛋白质印迹分别测量CR1和D1R途径中关键分子的基因和蛋白质水平。
结果：CSD降低海马CREB的基因和蛋白表达，SKF38393显着提高海马CREB的基因和蛋白表达（p <0.05）。 CSD使海马PKA的基因和蛋白表达均降低，而SKF38393则使PKA的基因和蛋白表达均显着提高（p <0.05）。 SKF38393可以显着改善CSD大鼠的CaMK IV基因水平和p-CaMK IV蛋白水平（p <0.05），但不能改善ERK1 / 2和p-ERK1 / 2的蛋白表达。
讨论：CSD可明显降低海马CREB的表达。作为关键分子，PKA和CaMK IV在D1R活化过程中改善海马过程中起着重要作用，并且在CSD期间可通过PKA和磷酸肌醇途径改善这一过程。

BACKGROUND & AIMS: :We examined the effect of transient forebrain ischemia of 2-, 3-, 4- and 5-min duration on the development of delayed neuronal death in field CA1 of the hippocampus in the gerbil whose brain temperature was maintained at 37 degrees C. Transient ischemia of 3- and 4-min duration caused almost the same maximal damage in field CA1 as observed in the gerbils subjected to 5-min ischemia. A detrimental factor inducing delayed neuronal death in field CA1 may be already set up during the first 3 min after the onset of ischemia in the gerbil whose brain temperature is maintained at normothermic levels.

背景与目标： ：我们研究了持续2分钟，3分钟，4分钟和5分钟的短暂性前脑缺血对大脑温度保持在37摄氏度的沙土鼠海马CA1区迟发性神经元死亡发展的影响。持续3分钟和4分钟的局部缺血在田野CA1中造成的最大损害几乎与遭受5分钟局部缺血的沙鼠所观察到的相同。沙鼠缺血发作后的前3分钟内，可能已经建立了导致CA1区域延迟神经元死亡的有害因素，其脑温保持在正常水平。

BACKGROUND & AIMS: :It has been suggested that stroke-prone spontaneously hypertensive rats (SHRSP) show vulnerability to neuronal damage following transient ischemia. To observe the effect of hydroxyl radicals on neuronal damage in the hippocampus of SHRSP during ischemia and recirculation, we measured the levels of 2,3-dihydroxybenzoic acid (2,3-DHBA), as a biological marker of hydroxyl radicals in the hippocampus of SHRSP, by high pressure liquid chromatography-electrochemical detection. The production of hydroxyl radicals in the hippocampus during the first 20 min of recirculation was a peak in all intervals. The changes in 2,3-DHBA levels during ischemia and recirculation in SHRSP were significantly higher than in Wistar-Kyoto rats. These results suggest that neuronal damage following ischemia and recirculation is, in part, caused by the increase in hydroxyl radicals during ischemia and recirculation.

背景与目标： ：已经表明，中风倾向性自发性高血压大鼠（SHRSP）在短暂性脑缺血后表现出对神经元损害的脆弱性。为了观察羟基自由基对SHRSP缺血和再循环过程中海马神经元损伤的影响，我们测量了2,3-二羟基苯甲酸（2,3-DHBA）的水平，该水平是大鼠海马中羟基自由基的生物学标记SHRSP，通过高压液相色谱-电化学检测。在再循环的前20分钟内，海马中的羟基自由基的产生在所有时间间隔内均达到峰值。 SHRSP缺血和再循环期间2,3-DHBA水平的变化显着高于Wistar-Kyoto大鼠。这些结果表明，缺血和再循环后的神经元损害部分是由于缺血和再循环期间羟自由基的增加所致。