Auditory cued spatial learning in mice

Spatial learning based on auditory cues was examined by C57BL mice in dry versions of the Morris water maze task in a dark room. One speaker was placed outside of the maze in the first task and two speakers emitting different sounds were placed outside the maze in the second task. The mice could learn the position of food in both tasks. Performance was disrupted when the auditory cue was removed, but they performed well when the position of the sound and food were shifted to a fixed spatial relationship. Results demonstrate the ability of auditory cued spatial navigation in mice.     

Aging impairs hippocampus-dependent long-term memory for object location in mice

The decline in cognitive function that accompanies normal aging has a negative impact on the quality of life of the elderly and their families. Studies in humans and rodents show that spatial navigation and other hippocampus-dependent functions are particularly vulnerable to the deleterious effects of aging. However, reduced motor activity and alterations in the stress response that accompany normal aging can hinder the ability to study certain cognitive behaviors in aged animals. In an attempt to circumvent these potential confounds, we used a hippocampus-dependent object-place recognition task to show that long-term spatial memory is impaired in aged mice. Aged animals performed similarly to young adult mice on an object recognition task that does not rely on hippocampal function.     

氯碘羟喹对癫痫小鼠海马神经元凋亡和学习记忆功能的保护作用

目的 研究氯碘羟喹对癫痫小鼠海马神经元凋亡和学习记忆功能的保护作用。 方法 采用匹罗卡品癫痫小鼠模型。实验动物根据给药方式分3组：对照组（生理盐水）、癫痫组（匹罗卡品+生理盐水）、氯碘羟喹组（匹罗卡品+氯碘羟喹）。金属自显影技术观察海马锌的分布;尼氏染色观察海马神经元形态和数量;免疫印迹检测海马Bcl-2和Bax表达;ELISA检测海马Caspases-9和Caspases-3表达;动物行为学观察自发性癫痫发作次数、发作级别和发作持续时间;T迷宫和Y迷宫检测学习记忆能力。 结果 氯碘羟喹组小鼠海马锌显著减少;神经元损伤减轻,细胞数量增多;Bcl-2表达增多,Bax、Caspases-9和Caspases-3表达减少,Bcl-2/Bax值增大;癫痫发作次数减少,发作级别降低,发作持续时间缩短,学习记记能力增强（P<0.01）。 结论 氯碘羟喹能保护小鼠海马神经元,改善学习记忆功能。     

Ghrelin对小鼠空间记忆和海马神经元突触及生长激素促分泌素受体表达的影响

目的 探讨Ghrelin对正常小鼠空间学习记忆能力和海马神经元突触及生长激素促分泌素受体（GHS-R）表达的影响。方法 8周龄小鼠 20只,随机分为实验组和对照组,分别腹腔注射Ghrelin和等量生理盐水,通过水迷宫实验检测小鼠的空间学习记忆能力,免疫组织化学实验检测海马Ghrelin受体GHS-R表达,并通过电子显微镜观察海马突触的超微结构变化。结果 水迷宫隐匿平台实验中,第2、3、4天,实验组小鼠的逃避潜伏期与对照组相比明显缩短（P <0.05）,跨越平台次数明显增加(P <0.05）,海马CA3和齿状回区GHS-R免疫阳性产物表达明显增强（P <0.05）,神经元突触数量明显增加（P <0.05）。结论 Ghrelin可能通过结合GHS-R,增加海马神经元突触数量,显著改善小鼠的空间学习记忆能力。     

大鼠海马结构在空间辨别性学习记忆时的突触形态可塑性的定量研究

目的　观察由空间辩别性学习记忆活动引致的大鼠海马结构的突触可塑性变化。方法　本研究继电子显微镜下 ,对空间辨别性学习记忆模型大鼠和对照大鼠海马结构内突触形态学的对比性观察之后 ,又对两组大鼠海马结构内突触复合体进行了体视学指标的测算。结果　模型组大鼠海马CA3区多形层内突触数密度 (77 81± 16 0 0 )个 / μm3、突触活性点膜面积 (0 0 37± 0 0 0 8) μm2 / μm3、突触小泡的数量 (16 9946 86± 195 92 5 8)个 / μm3、线粒体的体积 (1 70± 0 86 ) %和数密度 (8777 5 4± 2 0 2 0 32 )个 / μm3 均比对照组大鼠的大或多 ,对照组大鼠以上指标分别为 :(2 8 35± 1 31)个 / μm3、(0 0 15± 0 0 0 2 ) μm2 /μm3、(6 4380 2 7± 872 8 6 6 )个 / μm2 、(0 5 8± 0 35 ) %、(2 2 82 46± 72 7 6 9)个 / μm3,其差异有高度显著性 (P <0 0 1)。结论　正常生理活动也可引致神经发生突触可塑性变化 ;突触可塑性变化的形式不仅包括突触复合体各结构的增大同时包括突触数量增多 ;突触活性点膜面积增大 ;突触小泡的数量增多和体积增大 ;突触前膨大内线粒体数量增多和体积增大。     

锌对疼痛后学习记忆障碍小鼠海马神经元P53蛋白表达的影响

目的 探讨锌对第5腰椎（L5）脊神经结扎横切所致神经病理性疼痛（NPP）模型的学习记忆功能障碍及海马组织中P53表达的影响。方法 成年小鼠（C57/BL6）48只, 随机分为3组(n=16 ),对照组（con）,NPP组及高锌NPP组（Zn-NPP）。对照组仅暴露L5脊神经不结扎,NPP组施行L5脊神经左侧结扎横切（L L5-SNT）手术,Zn-NPP组施行左侧L5-SNT手术后饮用硫酸锌水溶液。3组术后第29 天进行Morris水迷宫实验测量小鼠空间学习记忆能力,水迷宫实验结束后,采用流式细胞术检测各组细胞凋亡率,采用免疫组织化学及免疫印迹法检测各组P53表达。结果 Morris水迷宫实验中,NPP组 (21.03±12.08)m/s,Zn-NPP组(16.97±8.59)m/s及con组(8.74±3.61)m/s,隐藏平台潜伏期逐渐缩短(P< 0.05), 并穿过平台所在象限的时间及路径占总游泳时间和总路径的比例逐渐增加(P< 0.05)。流式细胞术检测结果显示,con组（1.88%）,Zn-NPP（16.12%）及NPP组（33.17%）凋亡率逐渐增多(P< 0.05)。免疫组织化学结果显示,con组,Zn-NPP组及NPP组的P53阳性表达吸光度值在CA1区分别为 27.42±7.08、37.52±10.58及53.31±9.26;CA3区分别为29.51±8.31、36.21±7.91及56.71±8.09。 免疫印迹结果显示,con组,Zn-NPP组及NPP组的P53表达吸光度值分别为 0.12±1.01、0.37±1.13和0.86±1.22,吸光度值逐渐增多(P< 0.05)。 结论 锌可改善NPP后小鼠学习记忆能力。     

Loss of place specificity in hippocampal complex spike cells of senescent rat

Firing characteristics of “place” cells in dorsal CA1 of hippocampus were recorded from 5 young (10–14 months) and 5 old (25–29 months) Fischer-344 rats. Animals were trained to obtain food reward on a radial 8-arm maze. Entry to the arms was controlled by the experimenter so that all 8-arm were visited in random sequence from trial to trial. For each cell, 8 such trials were given (64 arm choices) in order that statistical reliabilty could be obtained for firing rates over the maze surface. Single unit activity and the animal's position on the maze were continuously monitored by digital computer. Twenty-seven cells from each age group were studied in this way. No statistically significant differences were found between age groups in unit spike height, width or firing rates. A large, statistically significant difference, however, was found in both spatial specificity and reliability of firing patterns from trial to trial. These results are discussed in terms of a possible deficit in spatial information processing in the older animals.     

Correlation of increased hippocampal Sumo3 with spatial learning ability in old C57BL/6 mice

Age-related impairment of learning and memory is a common phenomenon in humans and animals, yet the underlying mechanism remains unclear. We hypothesize that a small ubiquitin-related modifier (Sumo) might correlate with age-related loss of learning and memory. To test this hypothesis, the present study evaluated age-related spatial learning and memory in C57BL/6 mice (25 aged 7 months and 21 aged 25 months) using a radial six-arm water maze (RAWM). After the behavioral test, the protein expression of Sumo3 was determined in different brain regions using Western blotting. The results showed that the 25-month-old mice had longer latency and a higher number of errors in both learning and memory phases in the RAWM task than the 7-month-old mice. Compared to the latter, the former's level of Sumo3 protein was significantly increased in the dorsal and ventral hippocampus. For the 25-month-old mice, the number of errors and the latency in the learning phase negatively correlated with the Sumo3 level in the dorsal hippocampus. These results suggest that increased Sumo3 in the hippocampus may be correlated with spatial learning ability in old C57BL/6 mice.     

苯丙胺对大鼠行为、学习能力及海马CA3区突触素表达的影响

目的观察苯丙胺对大鼠行为、空间辨别性学习能力和海马CA3区突触素表达的影响。方法将45只健康雄性SD大鼠随机分为:正常对照组、生理盐水组和苯丙胺组。①苯丙胺组每天肌注0.5mg/kg苯丙胺1次;②生理盐水组即注射等体积生理盐水;③正常对照组不予任何处理。每组大鼠分14d、28d和42d三个时间段进行一般行为学、学习记忆能力及海马CA3区突触素表达的检测。结果①苯丙胺组大鼠在注射苯丙胺10d后出现直立、点头、狂躁等行为改变。正常对照组、生理盐水组均无此现象出现;②苯丙胺组大鼠空间辨别性学习记忆能力的影响,在第1、2个时间段与对照组的比未见组间差异,在第3时间段的平均运行时间和正确率比对照组的延长和降低(P<0.05)。③苯丙胺组大鼠海马CA3区突触素表达在第一阶段比对照组的减少,并随着用药时间的延长减少的更明显(P<0.05)。结论苯丙胺对空间辨别性学习记忆时大鼠行为及海马CA3区突触素表达有影响。     

Occlusal disharmony induces spatial memory impairment and hippocampal neuron degeneration via stress in SAMP8 mice

We examined the effect of occlusal disharmony in senescence-accelerated (SAMP8) mice on plasma corticosterone levels, hippocampal neuron number, and spatial performance in the water maze. The bite-raised condition was associated with an accelerated age-related decline in spatial memory, increased plasma corticosterone levels, and a decreased number of neurons in the hippocampal CA3 region. The findings suggest that the bite-raised condition in aged SAMP8 mice induces hippocampal neuron loss, thereby leading to senile memory deficits.     

大鼠海马和颞叶一氧化氮合酶阳性神经元在学习记忆时的表达

目的　对获得空间辨别性学习记忆大鼠的海马结构和颞叶皮质内一氧化氮合酶 (NOS)免疫阳性神经元系统的观察 ,为一氧化氮 (NO)在学习记忆活动中的作用提供形态学依据。方法　以经水迷宫训练获得空间辨别性学习记忆的大鼠为模型组 ,建立游水对照组和空白对照组。用免疫组化的方法观察 3组大鼠海马和颞叶的NOS阳性神经元的形态学特征及测定免疫反应阳性产物的光密度值 (OD )。结果　 (1)NOS阳性神经元在 3组大鼠海马和颞叶呈散在分布。在海马CA1、CA2、CA3、CA4及龄状回 (DG)都有少量分布 ,颞叶以Ⅱ、Ⅲ、Ⅴ、Ⅵ层分布为主。神经元胞体形态有锥体形 ,圆形或椭圆形 ,梭形3种。 (2 )模型组大鼠海马和颞叶皮质NOS阳性神经元较对照组明显增多。 (3)其免疫反应阳性产物的OD值也较对照组明显增大。结论　NOS阳性神经元形态发生了可塑性变化 ,参与了学习记忆     

Aging: effects on beta-carboline binding in hippocampal subfields

The CA1 and CA4/area dentata subfields of the hippocampus in young, mature and old rats were examined for age-related change in propyl beta-carboline-3-carboxylate (PrCC) binding. 3H-PrCC bound with high affinity (Kd = 0.82 nM) to one binding site when ethyl beta-carboline-3-carboxylate was used to delineate specific binding. An age dependent change in the maximum number of 3H-PrCC binding sites in the CA1 and CA4/area dentate subfields of the hippocampus were assessed by using a saturating (6 nM) concentration of 3H-PrCC. Although 3H-PrCC specific binding at a saturating concentration (6 nM) was significantly less in both the CA1 and CA4/area dentata subfields of the senescent rat, the magnitude of the decrease was greater in the CA1 region. In addition, the affinity of the 3H-PrCC binding site in both subfields probably did not vary significantly with age. Therefore, the CA1 and CA4/area dentate of the rat hippocampus may not only lose BZ1 receptors or the BZ1 receptor conformation with age, but the severity of receptor or receptor conformation loss varies with the subfield.     

Distinct patterns of hippocampal formation activity associated with different spatial tasks: a Fos imaging study in rats

Fos levels were measured in rats trained in one of two qualitatively different spatial memory tasks in a water maze. In one task, (landmark condition) rats found a submerged platform that was always 25 cm south of a visible landmark, the absolute position of the platform and landmark changing after every trial. In the other task (place condition), rats swam to a platform that remained in the same absolute position on every session, but changed session to session, with this task relying on the memory of allocentric cues. Despite matched swim times, the landmark condition resulted in higher levels of Fos in a wide range of cortical and subcortical sites, including the hippocampus and its connections. Structural equation modelling revealed two different patterns of hippocampal function. In the allocentric place task there was a significant association between Fos activity in the entorhinal cortices and the hippocampus proper, while in the non-allocentric landmark task this relationship was not present, but was replaced by a connection from the entorhinal cortices to the subiculum. Thus, the two different tasks engage two different modes of hippocampal activity as demonstrated by Fos expression.     

新生期大鼠接种卡介苗对空间学习能力和海马突触可塑性的影响

目的检测免疫接种卡介苗（BCG）后大鼠行为学,电生理,海马神经元树突棘的变化。为进一步研究疫苗接种对突触传递和学习记忆的影响提供依据。方法实验分为卡介组和对照组。新生Sprague-Dawley（SD）大鼠于出生24h内背部皮下接种卡介苗,对照组皮下注射等量的PBS。4周时水迷宫检测其行为学的变化,在体LTP测其电生理的变化,并使用基因枪散射DiI染料法检测海马神经元树突棘的变化。结果与其对照组相比,卡介组空间学习记忆能力明显增强：LTP结果显著优于对照组;海马神经元树突棘的密度以及蘑菇样（mushroom）增多。结论新生期成功接种疫苗可以提高大鼠突触传递的可塑性并促进其学习记忆能力。     

海马CA1区5-HT_(1A)受体调控PTSD大鼠空间记忆的作用

目的:观察创伤后应激障碍(PTSD)大鼠海马长时程增强(LTP)的变化以及5-羟色胺1A受体(5-HT_(1A)受体)和突触后致密物蛋白95(PSD-95)的表达,探讨5-HT_(1A)受体调控PTSD大鼠空间记忆的机制。方法:健康成年SD大鼠36只,随机分为正常对照组和模型组,每组18只。模型组采用连续单一刺激构建PTSD大鼠模型。Morris水迷宫实验检测2组大鼠的学习和记忆能力,电生理实验检测强直性高频刺激对海马LTP的影响Western blot法和免疫荧光实验检测海马5-HT_(1A)受体和PSD-95蛋白的表达。结果:Morris水迷宫实验结果显示在各实验日模型组大鼠逃避平台的潜伏期较对照组显著延长(P0.05)。电生理实验结果显示在强直性高频刺激后,2组大鼠海马诱发电位的幅值明显升高,模型组诱发电位的幅值显著低于对照组(P0.01)。Westem blot实验和免疫荧光实验结果显示,与对照组比较,模型组大鼠海马CA1区5-HT_(1A)受体的表达显著增加(P0.05),但PSD-95的表达明显减少(P0.05)。结论:PTSD大鼠空间记忆能力减退,可能与海马CA1区5-HT_(1A)受体的表达增加和PSD-95的表达减少有关。     

鱼油制剂中DHA对小鼠海马NOS阳性神经细胞表达的影响

目的　观察鱼油制剂中DHA(DecosahehexaenoicAcid)对小鼠海马一氧化氮合酶阳性神经元表达的概况。方法　实验动物分为三组 :剂量组、对照组和空白对照组。应用NADPH d组化法显示小鼠海马CA1、CA3 区和齿状回NOS(NitricOxideSynthase)阳性神经元及其数量、突起及透光率。结果　剂量组的NOS阳性神经元数量及透光率匀大于对照组和空白组 ,剂量组胞体深染 ,透光率值低 ,对照组和空白组胞体数量少 ,透光率值高。结论　DHA对小鼠神经系统的生长发育可能具有促进作用。     

Effects of fornix transection and cingulate cortical ablation on spatial memory in rhesus monkeys

Summary This study, together with a parallel study in rats (Markowska et al. 1988), attempted to relate the effects of hippocampal-system damage on similar tasks in both rats and monkeys. Not only were monkeys given a task (Experiment 1) which was of the sort usually used with rats, but in the companion study rats were given tasks (Experiment 2) like those usually used with monkeys. Experiment 1 examined the performance of rhesus monkeys with hippocampal-system damage on a spatial working memory task. Monkeys were trained preoperatively on delayed nonmatching-to-sample in a T-maze, placed into groups matched for their preoperative learning scores, and then received one of three treatments: 1) transection of the fornix; 2) ablation of the cingulate cortex; or 3) a sham operation. Monkeys with fornix transection were severely and significantly impaired, but monkeys with cingulate cortical ablations were not significantly impaired, relative to the controls. The results demonstrate that monkeys with fornix transection are severely impaired on a spatial working memory task requiring locomotion and, taken together with earlier work, suggest that the effect of fornix transection in both rodents and nonhuman primates is at least qualitatively similar (see Markowska et al. 1988). Experiment 2 assessed the role of the fornix and cingulate cortex in three conditional tasks in which the monkeys were provided with various spatial cues to indicate which one of two objects was rewarded. Both experimental groups were unimpaired, relative to the control group, on all three tasks, indicating that fornix transection does not produce a general impairment in place learning.     

The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes

The effect of life-long 60% ad lib food restriction on performance in two tasks involving spatial memory, the eight-arm radial maze and the Morris water maze, was studied in young and aged Fischer 344 rats. Restricted (R) and ad lib (AL) feeding groups were compared at 8, 16, and 24 months of age on both tasks. A 30-month-old R group was also tested in the Morris water maze. In the eight-arm maze, although 24-month-old animals performed more poorly than 8- and 16-month-old animals during the first week of testing, overall accuracy of performance did not vary significantly as a function of age. Twenty-four-month-old animals took longer to make 10 choices than did younger animals, and there was a significant interaction between feeding regimen and age, reflecting the fact that at the two younger ages, R groups performed more quickly than the AL groups. In the Morris water maze, both distance swum and time to find the platform increased with age. Life-long food restriction led to small but significant improvements in performance in the water maze in aged rats. R groups showed evidence for better retention over 24-hour intervals than did AL groups. By 30 months of age, however, R animals showed impaired performance relative to younger R groups. These differential findings on the two tasks, as they were used here, suggest that there was greater impairment with age on the spatial memory task requiring retention of information over long intervals than there was on the task primarily involving working memory within a trial. Life-long food restriction would appear to delay the impairments of age, but not prevent them.     

神经细胞黏附分子在学习记忆减退大鼠海马中的表达

目的探讨神经黏附分子(NCAM)细胞在学习记忆减退对大鼠脑海马组织中的表达。方法20只雄性SD大鼠随机分成模型组和对照组。建立学习记忆减退模型鼠,4周后行Y迷宫检测和基底前脑胆碱能神经元免疫组织化学染色验证模型成立;并对海马CA1和CA3区进行免疫组织化学染色,观察NCAM含量的变化。结果Y迷宫检测显示模型组大鼠学习记忆能力较正常组明显下降,免疫组织化学染色表明模型组胆碱能神经元数和NCAM阳性数明显低于正常组(P<0.05)。结论学习记忆减退可降低大鼠脑海马组织NCAM表达。     

Inhibitory effects of calcitonin gene-related peptide on long-term potentiation induced in hippocampal slices of rats

It is well known that hippocampus plays important roles in learning and memory. Both calcitonin gene-related peptide (CGRP) and CGRP receptors are found in hippocampus. In the present study we explored the influence of CGRP on long term potentiation (LTP) in hippocampal Schaffer collateral-CA1. Our results demonstrated that CGRP inhibited the LTP induced by high frequency stimulation (HFS) in hippocampal CA1 neurons in rat brain slices. The inhibitory effect was blocked by CGRP receptor-1 antagonist CGRP 8-37. The results indicate that both CGRP and CGRP receptor 1 are involved in the modulation process of LTP in hippocampus of rats.