Learning and memory disabilities in young adult rats from mildly zinc deficient dams

Three experiments were conducted to test the behavior of the offspring of rat dams (ZD) fed a mildly zinc deficient diet (10.0 micrograms Zn/g) during pregnancy and lactation. Since zinc deficiency causes anorexia, a second group of rat dams (PF) was fed the same quantity of the diet during gestation and lactation as was consumed by their ZD mates. A third group of rats (AL) was fed the diet ad lib during gestation and lactation. The PF and AL dams were given zinc supplemented (25.0 micrograms Zn/ml) drinking water whereas the ZD dams were given double distilled, deionized drinking water. After weaning, the offspring of all dams were fed Purina Laboratory Chow ad lib until they were 100 days old. The offspring were then reduced to 85% of their ad lib weight and tested on a 17-arm radial maze for memory and learning. In Experiments 1 and 2, the ZD males suffered a significant learning deficit when compared to the AL males. Whereas the PF males suffered a significant learning impairment in Experiment 1, the learning deficit of the PF group was not as severe as the deficit of the ZD group. There was no impairment in reference (long-term) memory for any of the groups. In Experiment 3, significant differences in working (short-term) memory were found among the three groups of females. The ZD group was significantly inferior in working memory when compared to the PF and AL groups. No significant differences in working memory were found between the PF and AL groups.     

Water maze performance and changes in serum corticosterone levels in zinc-deprived and pair-fed rats

The aims of the present study were (1) to evaluate the learning and short- and long-term memory of zinc-deprived (ZD) and pair-fed (PF) rats in a Morris water maze (MWM) and (2) to monitor the serum corticosterone levels of these rats before and after swimming. Young Sprague-Dawley rats (aged 27-31 days) consumed AIN-93G diet for 10 days, and then were separated into ad libitum control (CT), PF and ZD groups. The zinc content of the diet was 25-30 ppm (CT and PF) or <1 ppm (ZD). After 17 days on experimental diets, a MWM was used to test spatial cognition. Delayed-matching-to-place (DMP) test results indicate that both zinc deprivation and food restriction had no effect on short-term memory. The PF rats exhibited significantly impaired learning and thigmotaxia (i.e., wall hugging) in the learning test. The PF group also demonstrated less preference for the target zone in the first 15 s of the probing test. When the total 120 s of the probing test was considered, there were no differences in preference for the target zone, but thigmotaxia was greater in the PF than the CT group. The only behavioral change of the ZD group was thigmotaxia observed during the 120-s probing test following training, indicating the increment of anxiety. Morning basal corticosterone levels before swim training were significantly elevated in the PF group on Day 15 of dietary treatment, whereas a significant elevation of the basal corticosterone level in the ZD group was not statistically significant until Day 22. The data indicate an association between impaired learning, poor searching strategy and elevated corticosterone in the PF group. In contrast, the ZD rats showed normal cognitive performance but had elevated corticosterone and increased anxiety-like behavior (thigmotaxia).     

Mediodorsal thalamic lesions impair "reference" and "working" memory in rats

The present experiment evaluated the ability of rats with lesions in the thalamic mediodorsal nucleus (MD) to perform a task which differentiates between "reference" and "working" memory. In this task, only four of the arms of an 8-arm radial maze were baited, and animals were to restrict their entries to arms which were baited and to avoid never-baited arms. Despite several postoperative acquisition trials, rats with MD lesions did not acquire the task to a degree comparable to control subjects. Subjects with lesions continued to enter never-baited arms (reference memory errors) and to reenter baited arms (working memory errors). Given the lack of specificity in the behavioural impairment, the reference-working memory distinction seems to be an inappropriate one for characterizing the MD lesion deficit in rats. This deficit may involve an inability to use environmental stimuli to distinguish among arms of the maze, or an alteration in motor mechanisms.     

Short- and long-term components of working memory in the rat

Previous experiments suggested that working memory of rats trained on a radial maze can be discussed in terms of its short- and long-term temporal components. For example, in Mizumori, Channon, Rosenzweig, and Bennett's (1985) study, long-term working memory was found to be susceptible to disruption by the protein synthesis inhibitor anisomycin (ANI). In Experiment 1 of this report, we examined the neuropharmacological nature of short-term working memory of rats trained to retrieve food from all arms of a 12-arm radial maze. Delay intervals of varying length were placed between Choices 6 and 7. Lanthanum (LaCl3) and glutamate (GLU) injected bilaterally into the hippocampus effectively impaired retention over short delay intervals, which suggests a possible role for calcium and/or potassium and for glutamate in working memory. However, another equally likely explanation for the amnesic effects of LaCl3 and GLU is that these drugs impaired reference memory. To test more directly the hypothesis that LaCl3, GLU, or ANI might differentially affect working and reference memory, we tested the effects of these drugs on performance of rats trained to retrieve food from only 8 arms of the 12-arm maze in Experiment 2. The remaining 4 arms were never baited, in order to test reference memory function. We predicted that rats would make errors only in baited arms (i.e., errors of working memory). Instead, results of Experiment 2 showed that LaCl3, GLU, or ANI injection produced errors in unbaited arms even before a 120-min delay. If rats were injected with LaCl3 or GLU, baited-arm errors were observed only after the delay period.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of morphine dependence on the performance of rats in reference and working versions of the water maze

Numerous studies have dealt with the role of opiate system in tasks aimed at measurement of cognitive behavior, but the role of morphine dependence on learning and memory is still controversial. In this study chronic exposure to morphine was employed to evaluate learning ability and spatial short-term memory (working memory) and long-term memory (reference memory) in the water maze task. Male albino rats were made dependent by chronic administration of morphine in drinking water that lasted at least 21 days. In Experiment 1, the performance of animals was evaluated in reference memory version of the water maze. Rats were submitted to a session of 6 trials for 6 consecutive days to find the submerged platform that was located in the center of a quadrant. Latency and traveled distance to find the platform were measured as indexes of learning. Memory retention was tested 24 h after the last training session in a probe trial (60 s) in which there was no platform and the time spent in each quadrant of the water maze was recorded. Results indicated that latency and traveled distance to find the platform were same in control and dependent rats during training days, but during the probe test morphine-dependent group spent significantly less time in the target quadrant. In Experiment 2, training on working memory version of the water maze task was started. Only two trials per day were given until the performance of animals was stabilized (at least 5 days). Final test was done at day 6. Acquisition-retention interval was 75 min. No significant differences were found on acquisition and retention trials between morphine and control groups. Our findings indicate that chronic exposure to morphine did not impair learning ability, but partially impaired retention of spatial long-term (reference) memory. Moreover, dependence on morphine did not affect either acquisition or retention of spatial short (working) memory.     

锌对大鼠脾脏淋巴细胞功能的影响

通过大鼠锌（ＺＤ），过量锌（ＺＥ）模型，研究３锌对脾脏Ｔ、Ｂ淋巴细胞功能的影响，结果：①ＺＤ、ＺＥ组的脾重及脾脏指数，与对喂（ＰＦ）组、自由喂养（ＡＬ）组，缺锌后再补锌（ＺＤ＋ＡＬ）组比较，差别非常显著。②ＺＤ、ＺＥ组外周血白细胞减低，以淋巴细胞为主。③ＺＤ、ＺＥ组Ｔ、Ｂ淋巴细胞增殖率非常显著低于ＰＦ、ＡＬ和ＺＤ＋ＡＬ组。④ＺＤ、ＺＥ组的总脾淋巴细胞，Ｔ、Ｂ淋巴细胞细胞周期Ｇ０／Ｇ１％增高，而Ｓ％     

Performance on spatial working memory tasks after dorsal or ventral hippocampal lesions and adjacent damage to the subiculum

Rats with excitotoxic lesions of the dorsal or ventral hippocampus and control rats were trained on 2 spatial working memory tasks: the standard version of the radial maze with 8 baited arms and the non-matching-to-place procedure in the T maze. Dorsal lesions produced deficits in both tasks, whereas ventral lesions did not affect learning in either of them. A volumetric analysis of subicular damage showed that dorsal hippocampal lesions caused a deficit in the non-matching-to-place only when accompanied by damage to the dorsal subiculum; on the other hand, lesions to the dorsal hippocampus impaired performance in the radial-arm maze regardless of the extent of subicular damage.     

Intra-uterine nutrition and its effects on aggression

Prenatal zinc deficiency and prenatal undernutrition were found to have adverse effects on the food consumption and weight gain of pregnant dams and their offspring. Pups whose dams suffered prenatal zinc deficiency (ZD) consumed less food and gained less weight than pups whose dams suffered prenatal undernutrition (PF). The PF pups consumed less food and gained less weight than pups whose dams were normally fed (AL). The ZD females at age 75 days were significantly more aggressive than the PF females, while the PF females were more aggressive than the AL females. At age 105 days, ZD females were significantly more aggressive than the PF and AL females. There were no differences in aggression between the PF and AL females at 105 days. Among the ZD, PF, and AL male offspring, there were no differences in aggression at either age level except that the 75 day old PF males were significantly less aggressive than the AL males. Thus prenatal malnutrition, especially zinc deficiency, seems to have differential effects on the aggressive tendencies of female and male offspring.     

Maternal care affects male and female offspring working memory and stress reactivity

Variations in maternal care affect the development of individual differences in learning and memory and neuroendocrine responses to stress in adult male offspring, but it is not known how variations in maternal care affect adult female offspring. The present study investigated the performance of adult Sprague-Dawley male and female offspring exposed to either low or high levels of maternal licking/grooming on a spatial memory task (Experiment 1) and the effects of acute stress on corticosterone levels and spatial memory performance (Experiment 2). In Experiment 1 rats were trained for 24 days on the spatial working/reference memory version of the radial arm maze (RAM). In Experiment 2, rats were trained on the same RAM task, exposed to an acute stress, and the effect of stress on corticosterone levels and subsequent spatial memory was examined. In Experiment 1, adult female offspring of low licking/grooming dams had enhanced working memory compared to all other groups. In Experiment 2, all groups of male and female offspring had enhanced working memory 24 h after exposure to acute 2 h restraint stress while reference memory was enhanced after stress in male and female offspring of low licking/grooming dams. Furthermore, female offspring of low licking/grooming dams showed the largest corticosterone response to the acute restraint stress compared to all other groups. Male offspring of low licking/grooming dams showed a flattened corticosterone response to stress. Thus variations in maternal care differentially affect working memory and stress reactivity in male and female offspring.     

Reference and working memory of rats following hippocampal damage induced by transient forebrain ischemia

Acquisition of reference and working memory was evaluated in an animal model of cerebral ischemia. Rats were subjected to 30 minutes of transient forebrain ischemia, allowed to recover, and then tested for 95 trials on an 8-arm maze with 5 arms baited. During the 95 trials post ischemic (PI) rats made significantly more working and reference errors than controls (p less than 0.05). However, an analysis of the last 20 trials (75-95) showed that while PI rats and control rats had comparable reference memory (p greater than 0.8). PI rats tended to have a persistent working memory deficit compared to controls (p less than 0.06). Subsequent morphologic analysis showed that PI rats had almost complete loss of pyramidal neurons in the anterior CA1 region of the hippocampus, moderate to severe loss in mid-dorsal posterior hippocampus, and less damage to the dorsolateral striatum. These results suggest that the PI animal is a reasonable model for the permanent behavioral impairment and pathologic damage found in some human survivors of cardiac arrest.     

铅暴露对大鼠学习和记忆的影响

目的:研究低水平铅暴露对大鼠学习和记忆的影响。方法:0.05%水平醋酸铅污染大鼠饮用水28天,用Morris水迷宫试验测定大鼠的学习记忆功能。结果:在定位导航任务两组之间没有差异(P>0.05);在探索试验和工作记忆任务中,铅暴露组和正常对照组大鼠成绩显著差异(P<0.01)。结论:铅暴露对大鼠空间参考记忆和工作记忆有明显损害作用,对空间学习未见明显影响。     

Deficits in radial-arm maze learning in aged rats

The present study was designed to investigate the possible deficits in the place learning on the 8-arm radial maze in aged rats. In this task, reward was given in the 4 predetermined arms. Aged rats (27 months old, N = 7) acquired this task more slowly than young rats (12 months old, N = 11), and didn't reach to the performance level of the young rats within 80 training trials. Analysis of error choices revealed that the aged animals first entered in the unbaited arms more often than the young rats, whereas there was no difference in the number of re-entered choices to the baited and unbaited arms between the aged and young animals. Therefore, it was concluded that learning deficits in aged rats were attributed to deficits in the reference memory but not in the working memory.     

Chronic administration of docosahexaenoic acid improves reference memory-related learning ability in young rats.

Wistar rats were fed a fish oil-deficient diet through three generations. The young (five-week-old) male rats of the third generation were randomly divided into two groups. Over 10 weeks, one group was perorally administered docosahexaenoic acid dissolved in 5% gum Arabic solution at 300 mg/kg/day; the other group received a similar volume of vehicle alone. Five weeks after starting the administration, the rats were tested for learning ability related to two types of memory, reference memory and working memory, with the partially (four of eight) baited eight-arm radial maze. Reference memory is information that should be retained until the next trial. Working memory is information that disappears in a short time. Entries into unbaited arms and repeated entries into visited arms were defined as reference memory errors and working memory errors, respectively. Docosahexaenoic acid administration over 10 weeks significantly reduced the number of reference memory errors, without affecting the number of working memory errors, and significantly increased the docosahexaenoic acid content and the docosahexaenoic acid/arachidonic acid ratio in both the hippocampus and the cerebral cortex. In addition, the ratio demonstrated a significantly negative correlation with the number of reference memory errors. These results suggest that chronic administration of docosahexaenoic acid is conducive to the improvement of reference memory-related learning ability, and that the docosahexaenoic acid/arachidonic acid ratio in the hippocampus or the cerebral cortex, or both, may be an indicator of learning ability.     

Individual variation in the spatial reference and working memory assessed under allothetic and idiothetic orientation cues in rat

The present study was designed to examine which kind of memory: reference or working, better correlates with individual variation in rats' spatial learning abilities. To answer this question two groups of rats were trained to an arbitrary criterion in a partially baited 12-arm radial maze under two different experimental conditions: with or without allothetic cues. After 10 days break, rats were examined under the same conditions for memory retention. Within- and between-group variation in the length of training to criterion, and in the frequency of reference and working memory errors were analysed. The present experiment confirmed the facilitating effect of the presence of distal visual cues on place learning in rats. Task-dependent (between-group) differences in the rate of learning were attributed to differences in the frequency of reference memory errors. Conversely, within-group variation in the rate of task acquisition reflected individual variation in the frequency of working memory errors. These results were looked upon from an evolutionary perspective. Low correlation between reference and working memory errors confirms that these two types of memory have different mechanisms. The fact that differences in the rate of learning were not paralleled by the differences in the memory retention supports the notion that memory acquisition and memory retention are two independent processes.     

外源性神经节苷脂对大鼠脑内注入β-淀粉样蛋白导致的行为损伤的改善作用(英文)

本研究探讨了将β-AP分别注入大鼠海马、隔核和基底巨细胞核后学习和记忆功能的变化。行为测试在β-AP注入 1周后进行。双侧海马 (背部 )注入β-AP后 ,大鼠的分辨学习能力明显下降 ,对照组达到学会标准所需的次数为 2 5± 10 .7;而β-AP组为3 6.7± 9.8,两组差别非常显著 (P<0 .0 0 5 ) .在注射 β-AP后每天给予 40 mg/kg(i.p.)的神经节苷脂 (GAs) ,连续 6d,则大鼠的学习能力可明显改善 ,达到标准所需次数为 2 6.3± 9.2。隔核内注入 β-AP后大鼠的分辨学习能力没有明显的变化 ,而一次性平台测试成绩明显下降 ,同样外源性神经节苷脂可改善这种记忆功能的损伤。本研究还观察了 β-AP注入基底巨细胞核所造成的工作记忆损伤以及 GAs对其的改善作用     

Reward improves working memory of rats in the radial maze

The effect of reward on the formation and retention of short-term memory traces was examined in the radial maze. In Experiment 1, overtrained rats (n=12) made fewer errors (0.45 errors/trial) in an empty than in a baited 12-arm maze (1.19 errors/trial). In Experiment 2, two-min interval between the first six and second six choices only slightly increased error incidence in rewarded trials (1.33 errors/trial), but significantly deteriorated performance in non-rewarded trials (2.48 errors/trial). In Experiment 3, restricting the reward and non-reward conditions to the first six (R-N) or last six (N-R) choices of a trial only slightly impaired performance (about 1.5 errors/trial). In Experiment 4, rats were rewarded or non-rewarded in the first six choices made in maze A or in the second six choices performed in the similar maze B. The performances in the second six choices were close to chance in the AN-BN and AR-BN conditions (2.58 errors/trial) and intermediate in the AR-BR and AN-BR conditions (1.91 and 2.04 errors/trial, respectively). The positive effect of reward was not eliminated by the change of apparatus and cannot be due, therefore, to more intense scent marking. It is concluded that anticipated or accomplished consummatory activity improves efficiency of the working memory.     

Selective immunolesions of CH4 cholinergic neurons do not disrupt spatial memory in rats

Adult male Long-Evans rats were subjected to bilateral lesions of the cholinergic neurons in the nucleus basalis magnocellularis (NBM) by injection of 0.2 or 0.4 microg 192-IgG-saporin in 0.4 microl phosphate-buffered saline. Control rats received an equivalent amount of phosphate-buffered saline. Starting 2 weeks after surgery, all rats were tested for locomotor activity in their home cage, beam-walking performance, T-maze alternation rates (working memory), reference and working memory performance in a water-maze task, and memory capabilities in the eight-arm radial maze task using uninterrupted and interrupted (delay of 2 min, 2 h and 6 h after four arms had been visited) testing procedures. Histochemical analysis showed a significant decrease of acetylcholinesterase (AChE)-positive reaction products (30-66%) in various cortical regions at the 0.2-microg dose. At the dose of 0.4 microg, there was an additional, although weak, damage to the hippocampus (17-30%) and the cingulate cortex (34%). The behavioral results showed only minor impairments in spatial memory tasks, and only during initial phases of the tests (reference memory in the water maze, working memory in the radial maze). The behavioral effects of the dramatic cholinergic lesions do not support the idea of a substantial implication of cholinergic projections from the NBM to the cortex in the memory processes assessed in this study, but they remain congruent with an involvement of these projections in attentional functions.     

Retrograde amnesia for fear-potentiated startle in rats after complete,but not partial,hippocampal damage

We assessed the involvement of the hippocampus in recall of learned fear of a discrete visual stimulus using a fear-potentiated startle (FPS) procedure. Recall was measured by an increase in acoustic startle in the presence of a light that was paired with footshock. In Experiment 1, rats either received sham, dorsal, ventral, or complete (dorsal and ventral) NMDA-induced damage of the hippocampus following FPS acquisition. During the post-surgery retention test, only the rats with complete hippocampal damage showed a significant FPS deficit. In Experiment 2, we examined whether recent and remote memory for FPS would be differentially affected by complete hippocampal damage. Rats received sham or complete hippocampal damage 1- or 4-wk after FPS acquisition. During the retention test, sham rats exhibited significant FPS, whereas rats with hippocampal damage showed a large FPS deficit that was equivalent for recent and remote memories. In Experiment 3, we found that rats with complete hippocampal damage induced before conditioning showed levels of FPS that did not significantly differ from sham rats. Combined, these findings suggest that extensive damage to the hippocampus causes retrograde amnesia for a memory involving a light–shock association that is not temporally graded. The same damage does not cause anterograde amnesia in the same memory task. Partial damage of the hippocampus, whether of the dorsal or ventral region, was insufficient to cause retrograde amnesia. Thus, the hippocampus normally has a critical and long-lasting role enabling recall of fear conditioning to a discrete visual stimulus. In the absence of the hippocampus other memory systems support new learning.     

缺锌对大鼠海马结构含生长抑素mRNA神经元的影响

要采用缺锌饲料喂养动物四周后，用原位杂交组织化学结合图象分析技术，研究了缺锌大鼠海马结构内含生长抑素mR-NA神经元的变化。并采用原子吸收分光光度计测定血浆锌含量。结果与对照组相比.缺锌大鼠血浆锌含量明显降低（P＜0.05），海马和齿状回合生长抑素mRNA的神经元数目明显减少（P＜0.01），胞体的灰度值明显降低（P＜0.01），而胞体的截面积无明显改变。结果提示，缺锌时，海马结构生长抑素mRNA的表达下调，海马结构神经元合成生长抑素的能力降低。这种变化可能是缺锌影响脑的学习记忆功能的重要原因之一。     

Impairment of recognition memory and hippocampal long-term potentiation after acute exposure to clioquinol

Clioquinol (CQ) was associated with cases of transient global amnesia and with the neurodegenerative syndrome subacute myelo-optico-neuropathy (SMON) in humans. However, CQ forms lipophilic chelates with cations and has the potential as a scientific and clinical tool used for selective modulation of histochemically reactive zinc pools. The relationship among transient lack of synaptic zinc release, hippocampal long-term potentiation (LTP) induction and cognitive memory is poorly understood. To evaluate the role of synaptic zinc release, in the present study, hippocampal LTP induction and cognitive behavior were examined in young rats after i.p. injection of CQ (30 mg/kg). Intracellular zinc detected by Timm's stain and extracellular (synaptic cleft) zinc detected by ZnAF-2 were significantly decreased in the hippocampus 6 h after CQ injection. The molecular layer of the dentate gyrus, in which perforant path-granule cell synapses exist, was most responsive to CQ injection. Dentate gyrus LTP was induced similarly to the control 2 h after CQ injection, while significantly attenuated 6–24 h after CQ injection. In the training trial of the object recognition memory 2 h after CQ injection, there was no significant difference in learning behavior between the control and CQ-treated rats. In the test trial, CQ-treated rats showed normal recognition memory 1 h after the training, whereas recognition memory deficit 24 h after the training unlike the control rats. These results indicate that acute exposure to CQ impairs long-term (24 h) memory in the hippocampus of young rats. The CQ-mediated attenuation of dentate gyrus LTP, which may be associated with the transient lack of zinc release from zincergic neurons, seems to be involved in the impairment of the long-term memory.