磁场对小鼠两种迷宫学习记忆的影响

据发现,磁场对生物体有一定作用,但是磁场对于人类或实验动物的学习记忆是否有影响,目前的报道结果很不一致。本实验采用实验小白鼠,给予不同强度（65高斯／50Hz,35高斯/25Hz）的低频磁场照射（每天1小时,持续25天）。磁场照射后,采用旷场行为测试、Y-迷宫和Morris水迷宫,检测小鼠的活动性、空间辨别、空间学习记忆和非空间学习记忆能力。结果表明：65高斯／50Hz磁场显著增高小鼠的活动性,并损伤小鼠Y-迷宫的空间辨别能力,但对Morris水迷宫的空间、非空间学习记忆无明显影响。35高斯／25Hz磁场处理动物行为在三个指标上均接近对照组。提示：长期的磁场照射可能会给动物,甚至人类造成一些影响。     

Paradoxical effects of learning the Morris water maze on adult hippocampal neurogenesis in mice may be explained by a combination of stress and physical activity

Studies in rats that assessed the relation of hippocampus-dependent learning and adult hippocampal neurogenesis suggested a direct regulatory effect of learning on neurogenesis, whereas a similar study in mice had not found such causal link. We here report a substantial decrease of BrdU-positive cells and other measures of adult hippocampal neurogenesis in mice trained in the hidden (HID) or cued version (VIS) of the Morris water maze as compared to untrained animals (CTR). Particularly, cells on advanced stages of neuronal development contributed to this decrease, whereas earlier progenitors (type 2 cells) were not diminished in HID, but were diminished in VIS as compared to CTR. The differential regulation of type 2 cells in HID and VIS may have been caused by a different degree of physical activity, given that a time-yoked control group did not differ from HID, and type 2 cells reportedly constitute the proliferative dentate gyrus population that primarily responds to physical activity. The decrease of hippocampal neurogenesis by water maze training was reversible by pre-exposing animals to the water maze prior to training, suggesting that stress associated with training may have caused the acute downregulation of adult neurogenesis. We propose that in mice the Morris water maze does not provide a pure enough learning stimulus to study the presumed effects of 'learning' on adult neurogenesis. In addition, however, our data show that physical activity that is intricately linked to many cognitive tasks in rodents might play an important role in explaining effects of learning on cellular hippocampal plasticity.     

Effects of dietary restriction on physical performance in mice

Dietary restriction is known to prolong life in laboratory animals. However, little is known about the effects of dietary restriction on physical performance. To evaluate physical performance, we measured four item indices: time to climb out of obstacles, time to escape restraint by gummed tape, time hanging from a bar, and ability to resist slipping every week. The diets of ICR mice were restricted from the age of 7 weeks through 24 weeks. Body weight of the diet-restricted mice decreased during the 7th to 9th weeks of age. After the 10th week, weight gain resumed. In response to assigned tasks, the diet-restricted mice performed better in all activities: they climbed out of obstacles faster, freed themselves sooner from restraint by gummed tape, hung from a bar longer, and better resisted slipping down a slope. These results suggest that diet-restricted mice have superior physical abilities, such as those required to overcome or avoid risks to life, than do ad-libitum-fed mice.     

Neonatal exposure to intermittent hypoxia enhances mice performance in water maze and 8-arm radial maze tasks

Hypoxia has generally been reported to impair learning and memory. Here we established a hypoxia-enhanced model. Intermittent hypoxia (IH) was simulated at 2 km (16.0% O2) or 5 km (10.8% O2) in a hypobaric chamber for 4 h/day from birth to 1, 2, 3, or 4 week(s), respectively. Spatial learning and memory ability was tested in the Morris water maze (MWM) task at ages of postnatal day 36 (P36)-P40 and P85-89, respectively, and in the 8-arm maze task at P60-68. The long-term potentiation (LTP), synaptic density, and phosphorylated cAMP-responsive element-binding protein (p-CREB) level in the hippocampus were measured in mice at P36 under the IH for 4 weeks (IH-4w). The results showed that IH for 3 weeks (IH-3w) and IH-4w at 2 km significantly reduced the escape latencies of mice at P36-40 in the MWM task with significantly enhanced retention, and this spatial enhancement was further confirmed by the 8-arm maze test in mice at P60-68. The improvement in MWM induced by IH-4w at 2 km was still maintained in mice at P85-89. IH-4w at 2 or 5 km significantly increased amplitude of LTP, the number of synapse, and the p-CREB level in the hippocampus of P36 mice. These results indicated that IH (4 h/day) exposure to neonatal mice at 2 km for 3 or 4 weeks enhanced mice spatial learning and memory, which was related to the increased p-CREB, LTP, and synapses of hippocampus in this model.     

Effect of L-asparaginase on retention of maze learning in mice

Long-term memory impairment has been described previously in mice receiving inhibitors of protein synthesis. In the present work, the enzyme L-asparaginase was injected into mice by an intrathecal or by an intraperitoneal route and produced a significant impairment of memory. Glutamine and asparagine prevented the effect of asparaginase when injected by the intraperitoneal route.     

Acquisition of dominance status affects maze learning in mice

Learning is likely to be costly and thus subject to trade-off with other components of life history. An obvious prediction, therefore, is that investment in learning, and thus learning performance, will vary with individual life history strategy and the reproductive value of the learning outcome. We tested this idea in the context of social dominance in male laboratory mice, using a simple radial maze paradigm to compare the ability of high- and low-ranking male mice to track changing food location. We tested animals in randomly selected pairs before and after establishing aggressive rank relationships to distinguish intrinsic differences in learning ability from those attributable to acquiring high or low rank. There was no difference in learning between later dominants and subordinates prior to establishing rank relationships. After pairing, however, dominants showed a significantly greater percentage of correct responses, with the difference being greatest earlier in a sequence of trials. The percentage of correct responses also increased with the amount of aggression initiated during pairing. The results thus appeared to reflect a state-dependent change in learning associated with the aggressive social relationships formed during pairing.     

Effects of nucleotides on learning and memory in a Morris water maze test in normal and basal forebrain-lesioned rats

The effects of nucleotides on learning and memory were studied in normal and basal forebrain-lesioned rats using a Morris water maze test. Chronic oral administration of a nucleotide mixture (500 mg/kg), containing an equal weight of the disodium salts of adenosine 5'-monophosphate, guanosine 5'-monophosphate, inosine 5'-monophosphate, cytidine 5'-monophosphate, and uridine 5'-monophosphate facilitated learning acquisition in normal rats. In basal forebrain-lesioned rats, administration of the nucleotide mixture showed a tendency to improve learning acquisition and memory retrieval. In the biochemical studies, no significant changes were observed in brain choline and acetylcholine levels by treatment with the nucleotide mixture at the doses tested in both normal and basal forebrain-lesioned rats. The nucleotides did not affect the monoaminergic systems in normal rats, but did cause some changes in these systems in basal forebrain-lesioned rats. The present studies indicate that nucleotides ameliorate learning and memory processes in normal rats, but not in basal forebrain-lesioned rats, and they also modulate the activity of the central monoaminergic systems under certain conditions.     

Effects of estrogens on learning of rats with chronic brain cholinergic deficit in Morris water maze

A chronic deprivation of brain cholinergic functions in rats caused by intracerebroventricular injection of neurotoxin AF64A increases the escape latency in Morris water maze test as compared to control sham-operated animals. Measurements and analysis of rat movement tracks using an original computerized "Behavioral Vision" system revealed the ability of 17 beta-Estradiol and its synthetic isomer J-861 (both administered daily in per os dose 0.2 mg/kg during 7 days before and 10 days after a single intracerebroventricular injection of AF64A) to improve learning of the animals. Directivity of search trajectories was estimated by a novel index of track straightness. The introduction of an index of "passive swimming" made it possible to reveal episodes of immobility in water-maze behavior of AF64A-injected animals. Unlike J-861, 17 beta-Estradiol almost completely eliminated these episodes. The newly developed indices (especially straightness) seem to be very useful in differentiating learning ability of rats from a decrease in their mobility in the Morris water-maze test, in particular, in case of the estrogens under study.     

Pre-natal administration of diazepam improves radial maze learning in mice

A number of studies have found that the peri-natal exposure of rodents to diazepam alters their adult behaviour. Adult male mice, treated with diazepam or appropriate controls during pregnancy, were examined in terms of their ability to learn a radial maze. Those animals receiving diazepam prior, but not after birth, learnt the maze significantly more rapidly. The results are discussed in terms of the possible involvement of the hippocampus in this influence of diazepam.     

Lack of protection of monoamine oxidase B-deficient mice from age-related spatial learning deficits in the Morris water maze

Monoamine oxidase B (MAO-B) increases in brain in response to aging and neurodegeneration. Whether such increases represent a risk factor to further neuronal damage or simply represent epiphenomena remains unclear. L-deprenyl, an inhibitor of MAO-B, has been shown to improve learning in aged rodents. However, recent data suggests this may occur through mechanisms independent of its enzymatic inhibition. This study investigates visualspatial learning of MAO-B deficient mice and examines what effects absence of MAO-B has on age-related cognitive decline. Learning was tested in the Morris Water Maze in male transgenic MAO-B knockout mice (KO) ages 2 months (n = 9), 7 months (n = 7), and 17 months (n = 8). Performance was compared to that of wild type (WT) littermates. Animals were given four 60 second trials per day with the submerged platform in the "North" position. Animals received 7 days of learning in which they were introduced into the pool facing the wall, alternating between the "East" and "West" positions. A single probe trial followed on day 8, followed by continuation of the original learning paradigm on days 9 and 10. Subsequently, the platform position was changed to the diagonally opposite quadrant and learning continued on days 11-13, followed by a cue phase in which the platform was made visible. Total distance traveled and latency to the platform was increased in 7- and 17- month old mice, most significantly at the beginning of the acquisition phase. This effect reappeared again in 17- month old mice during the reversal phase. No predominant genotypic differences in latency or distance were observed during any phase of the experiment. Our results show that presence or absence of MAO-B does not appear to alter performance in the Morris water maze. Furthermore, presence or absence of MAO-B does not provide protection from the age-dependent deficits in spatial learning.     

Two-day radial-arm water maze learning and memory task; robust resolution of amyloid-related memory deficits in transgenic mice

The radial arm water maze (RAWM) contains six swim paths (arms) extending out of an open central area, with an escape platform located at the end of one arm (the goal arm). The goal arm location remains constant for a given mouse. On day 1, mice are trained for 15 trials (spaced over 3 h), with trials alternating between visible and hidden platform. On day 2, mice are trained for 15 trials with the hidden platform. Entry into an incorrect arm is scored as an error. The RAWM has the spatial complexity and performance measurement simplicity of the dry radial arm maze combined with the rapid learning and strong motivation observed in the Morris water maze without requiring foot shock or food deprivation as motivating factors. With two sessions each day, 16 mice can be tested over 2 days.     

Learning to solve a spatial task in a water maze in aggressive and submissive mice

Learning and retention of the spatial memory were studied in mice with alternative under conditions of various experimental protocols. Visible and hidden platform acquisition in a simple model of the water maze was similarly fast both in aggressive and submissive mice, but extinction differed. Retention of the platform location preference persisted in aggressive mice in four testing trials. In submissive mice, extiction of the spatial memory was accompanied with a prolongation of search with parallel production of episodes of "passive drift". Differences in spatial learning between aggressive and submissive mice were revealed in a water maze complicated with partitions. In this case, aggressors were able to learn the position of a hidden platform (in contrast to submissive mice with the dominant response of "passive drift"). During testing the response, aggressive mice longer retained the spatial preference without extinction.     

紫皮石斛抗小鼠体力疲劳作用

目的:研究紫皮石斛对小鼠的抗体力疲劳作用。方法:取雄性昆明种小鼠50只,按体重随机分成5组(n=10):空白对照组,人参皂苷组,紫皮石斛高、中、低剂量组。空白对照组给予等体积的生理盐水,人参皂苷组给药剂量为200 mg/kg·d^-1,紫皮石斛高、中、低剂量组给药剂量分别为35.04 g/kg·d^-1生药、17.52 g/kg·d^-1生药、8.76 g/kg·d^-1生药,每天灌胃1次,连续15 d。于末次给药后30 min,测定小鼠负重力竭游泳时间及体内血清尿素氮、血清乳酸、肝糖原的含量,评价紫皮石斛的抗体力疲劳作用。结果:与空白对照组比较,紫皮石斛能延长小鼠负重游泳力竭时间,能降低小鼠游泳后的血清尿素氮、血清乳酸的含量,能提高小鼠体内肝糖原的储备量,且差异有统计学意义(P<0.05,P<0.01)。结论:紫皮石斛具有抗体力疲劳作用。     

Effects of cold on activity and exploration by wild house mice in a residential maze

Summary Wild house mice,Mus musculus, were bred in environments kept at 23 °C (warm-reared) or 3 °C (cold-reared). Males of the fourth generation in each condition were observed for 4 days in a residential maze with a central nest box and four arms radiating from it. One maze arm contained food, one contained water, and two were empty until Day 4, when one had soft (balsa) wood. Mice of each type were run in a maze at each temperature.Mice of all classes responded to the novel environment of the maze with a high rate of visiting the arms on Day 1. The novel presence of balsa wood also provoked extra visits to the arm that contained it, and a longer stay in that arm on Day 4 than on Day 3. Visits to the arms were fewer in the cold than in the warm, and time spent in the arms was less.Cold-reared mice in the cold environment spent more time outside the nest on Day 1, that is, were more responsive to novelty than were the warmreared. Hence for the cold-reared mice the competitive balance between exploring and energy conservation was altered. This difference, we suggest, is an aspect of cold-adaptation.These experiments were done in part while JLW held an award from the National Science Foundation under the US/Australia Agreement for Scientific Cooperation. We are also grateful to Rhondda G. Dickson for help with the statistical analysis.     

Effect of circadian phase on performance of rats in the Morris water maze task

The authors examined spatial working memory in the Morris water maze during the activity and rest periods of Wistar rats. Wheel-running activity was measured continuously as a marker of circadian phase. To minimize possible masking effects on performance, animals were placed in constant dim light the day before testing and tested in similar light conditions. Three experiments were run, each of them using animals varying in their previous experience in the water maze. Half of the animals of each experiment were tested 2 to 3 h after activity onset (active group), and the other half were tested 14 to 15 h after activity onset (inactive group). In the three experiments, a significant phase effect was observed in the animals' performance in the water maze; animals tested in the active phase showed steeper acquisition curves. These phase effects on performance are due to the animals' search pattern and not to a better acquisition and maintenance of spatial information; rats tested in the inactive phase found the platform faster on the first trial of the test, when the information on the location of the platform had not been presented to the animals. This effect vanished as the amount of training in the pool increased. Finally, swimming speed also showed a temporal effect, suggesting the existence of a phase effect for motivation to escape from the water; rats tested during their inactive phase tended to swim faster. All together, the data suggest a modulating effect of the biological clock on performance in the water maze, particularly when the animals are less experienced.     

Effects of estrogen and progesterone treatment on rat hippocampal NMDA receptors: relationship to Morris water maze performance

Estrogen modulates NMDA receptors function in the brain. It increases both dendritic spine density and synapse number in the hippocampus, an effect that can be blocked by NMDA antagonist. In this study, we investigated the effect of 17beta-estradiol and progesterone treatment on NMDA receptors in ovariectomized rats. Two different doses were used for 10 weeks. Receptor autoradiography was done on brain sections using [(3)H] MK-801 as a ligand. Our results showed a significant increase in [(3)H] MK-801 binding in the dentate gyrus, CA3 and CA4 areas of the hippocampus of ovariectomized compared to sham operated rats. In addition, we observed similar changes in CA1. 17beta-estradiol treatment in both doses reduced the binding back to the normal level while progesterone treatment did not show any effect. Spatial reference memory was tested on Morris water maze task. Ovariectomy severely impaired spatial reference memory. Estradiol but not progesterone treatment significantly improved the memory performance of the ovariectomized rats. Low dose treatment showed better learning than high dose estrogen treatment. The decrease in the antagonist sites by estradiol treatment could result in an increase in the sensitivity of the hippocampus to the excitatory stimulation by glutamate system and hence the effect of estradiol on learning and memory. The changes of NMDA receptors in the hippocampus support the concept that estrogen-enhancing effect on spatial reference memory could be through the enhancing of NMDA function.     

The effect of a caudal hippocampus lesion on learning in a Morris water maze in Bank Voles (Clethrionomys glareolus)

The involvement of the caudal hippocampus in spatial learning is presently uncertain, compared to the well established role of the dorsal region. Therefore voles (Clethrionomys glareolus) with large (about 1/3 of the whole hippocampus) caudal cytotoxic lesions were tested in the Morris water maze. A version of the test intended to measure long term spatial memory was used. The lesion inhibited the learning process, as well as reducing the accuracy of platform location memory at early stages of training. The data obtained indicate the involvement of this area in control of spatial learning in rodents.     

Sleep deprivation effect upon spatial memory consolidation in rats after one-day learning in a Morris water maze

The effect of sleep deprivation by 'carousel' method on spatial memory consolidation in a Morris water maze was studied in Wistar male rats after one-day learning (in accordance to a protocol by Frick et al., 2000). It was found that after fast 3-hr learning the memory trace retains during 24-hr. Twenty four hour sleep deprivation followed learning impaired consolidation of spatial memory. So the rat model of a one-day learning is suitable for the studying of neurophysiological mechanisms of sleep deprivation effects on spatial memory consolidation.