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.     

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.     

Effects of physical fatigue in mice on learning performance in a water maze

We investigated the effects of physical fatigue produced by swimming exercise on learning the Morris water maze in BALB/c mice. We measured the escape latency in the maze immediately after the swimming exercise. The control group was soaked in the water but not fatigued. For easier tasks, like one with an obvious cue flag, the escape latency was not changed by exercise fatigue. However, escape latency was increased after exercise fatigue for more difficult tasks of spatial learning. These results appear to suggest that physical fatigue impaired learning performance. The effects of swimming exercise fatigue on learning efficiency were then investigated. Mice were continuously fatigued during the spatial learning period. This increased escape latency between the first and third sessions. The results suggest that learning efficiency was impaired by exercise fatigue. This system may be useful for screening new foods used to enhance brain function during exercise.     

Social isolation improves working memory at reversal but not primary radial-arm maze learning in rats

Social isolation starting from the 21st day of birth affected neither a short-term nor a long-term memory in male rats at primary acquisition learning in an 8-arm radial maze. A number of the short-term and long-term memory errors were substantially decreased during primary learning but the difference between groups was not significant. Isolates were faster to start a search in an individual trial and took less time to finish offa trial. During the reversal learning, when baited and non-baited arms were reversed, the isolates outperformed of socially reared rats on working but not reference memory task. In overall they made twice less working memory errors than socially reared animals. During the reversal learning the isolates were also faster than non-isolates in initiation and completion of a trial. Maternal separation of rat's pups on the postnatal days 1-21 for 4 hr per day did not affect either working or reference memory on both primary and reversal learning. The data obtained are discussed on basis of influence of stress in early postnatal life on hypothalamo-pituitary axis and its effects on behavior of adult animals.     

Behavioral tactics among rats in a radial maze

The experiments were carried out on rats of Wistar (W) and Krushinsky-Molodkina (KM) lines, differing in the level of task performance in conditions of multiple choice of food sources in a 12ray radial symmetrical maze. It is shown that in the radial maze, the rats of both lines use a number of behavioural tactics. To determine the influence of changes of environmental spatial characteristics while preserving the main experimental strategy--never revisit the places of reinforcement,--on the peculiarities of tactics manifestations maze modifications were elaborated. Besides the environmental procedure was changed. Under all conditions the rats of W line solved the task. According to the situation, they either preserved former tactics or developed some new ones. The rats of KM line could not solve the task in changed conditions. In most sessions, appearance or absence of given tactics was not adequate to new conditions. The presence of the necessary tactics not always facilitated the task solving. Thus, for the realization of adequate reactions, the presence of necessary tactics is not sufficient: their "tuning" is needed depending on situation. The possibility is supposed of genetic determination of rats ability to some tactics. However, it is emphasized, that tactics are not strongly fixed, as their realization depends on environmental conditions.     

Long-term administration of maxadilan improves glucose tolerance and insulin sensitivity in mice

Maxadilan and its truncated variant, M65, are agonist and antagonist specific, respectively, for the PAC1 receptor. PAC1 is the specific receptor for the pituitary adenylate cyclase-activating peptide (PACAP), which is not shared by vasoactive intestinal peptide (VIP). PACAP is a ubiquitous peptide of the glucagon superfamily that is involved in glucose homeostasis and regulation of insulin secretion. This study employed the recombinant maxadilan and M65 to evaluate the PAC1 receptor-mediated effects on energy metabolism using NIH mice. First, the acute effect of maxadilan-induced hyperglycemia was blocked by M65. In long-term studies, NIH mice were given daily intraperitoneal injections with maxadilan, M65, or vehicle for 21 days. Maxadilan suppressed feeding and enhanced water intake significantly for the first several days. After that period, maxadilan treatment continued to promote food and water intake. Long-term administration of maxadilan led to an increase in body weight (P<0.01), decrease in body fat (P<0.01), down-regulation of basal plasma glucose (P<0.01), upregulation of basal plasma insulin (P<0.01) and improved glucose tolerance (P<0.01) and insulin sensitivity (P<0.01). An elevation in plasma LDL (P<0.01) was also observed in the maxadilan group. However, M65 displayed no significant adverse effects on the aforementioned parameters except basal plasma glucose (P<0.05). The significant changes induced by maxadilan indicate that the PAC1 receptor plays multiple key roles in carbohydrate metabolism, lipid metabolism and energy homeostasis in mice.     

DHEAS improves learning and memory in aged SAMP8 mice but not in diabetic mice

Dehydroepiandrosterone sulfate (DHEAS) has been reported to improve memory in aged animals and suggested as a treatment for age-related dementias. The SAMP8 mouse, a model of Alzheimer's disease, has an age-related impairment in learning and memory and an increase in brain levels of amyloid precursor protein (APP) and amyloid beta protein (Abeta). Male SAMP8 mice also have a decrease in testosterone, to which DHEA is a precursor. Diabetes has been suggested as a model of aging and to be linked to Alzheimer's disease. Diabetics can have memory deficits and lower DHEAS levels. Here, we examined the effects of chronic oral DHEAS on acquisition and retention for T-maze footshock avoidance in 12 mo male SAMP8 mice and in CD-1 mice with streptozocin-induced diabetes. Learning and memory were improved in aged SAMP8 mice, but not in CD-1 mice with streptozocin-induced diabetes. These findings suggest that DHEAS is more effective in reversing the cognitive impairments associated with overexpression of Abeta than with diabetes.     

Contextual control of rats' foraging behaviour in a radial maze

This study demonstrated that with experience rats were able to discriminate the background contextual cues in order to foraging correctly in an eight-arm radial maze if the background contexts signaled to the rats which of two bait patterns was in effect in that context. Four of the eight arms were context-dependent: two arms were baited in the "night" context, while the other two were baited in the "daytime" context. The remaining four arms were context-independent: three of them were never baited, while the remaining one was baited in both contexts. The rats gradually began to avoid the arms that were uniquely baited in the other context, suggesting a contextual or conditional control of arm selection. Interestingly, these rats also showed better performance in avoiding the never-baited arms, compared with control rats. Namely, disambiguating the incentive values of the four arms by contextual cues collaterally facilitated the context-independent arm performance. Another interesting finding of the present study is that the rats did not visit the always-baited arm earlier than the arms uniquely baited in that context.     

Catechin treatment improves cerebrovascular flow-mediated dilation and learning abilities in atherosclerotic mice

Severe dyslipidemia and the associated oxidative stress could accelerate the age-related decline in cerebrovascular endothelial function and cerebral blood flow (CBF), leading to neuronal loss and impaired learning abilities. We hypothesized that a chronic treatment with the polyphenol catechin would prevent endothelial dysfunction, maintain CBF responses, and protect learning abilities in atherosclerotic (ATX) mice. We treated ATX (C57Bl/6-LDLR(-/-)hApoB(+/+); 3 mo old) mice with catechin (30 mg · kg(-1) · day(-1)) for 3 mo, and C57Bl/6 [wild type (WT), 3 and 6 mo old] mice were used as controls. ACh- and flow-mediated dilations (FMD) were recorded in pressurized cerebral arteries. Basal CBF and increases in CBF induced by whisker stimulation were measured by optical coherence tomography and Doppler, respectively. Learning capacities were evaluated with the Morris water maze test. Compared with 6-mo-old WT mice, cerebral arteries from 6-mo-old ATX mice displayed a higher myogenic tone, lower responses to ACh and FMD, and were insensitive to NOS inhibition (P < 0.05), suggesting endothelial dysfunction. Basal and increases in CBF were lower in 6-mo-old ATX than WT mice (P < 0.05). A decline in the learning capabilities was also observed in ATX mice (P < 0.05). Catechin 1) reduced cerebral superoxide staining (P < 0.05) in ATX mice, 2) restored endothelial function by reducing myogenic tone, improving ACh- and FMD and restoring the sensitivity to nitric oxide synthase inhibition (P < 0.05), 3) increased the changes in CBF during stimulation but not basal CBF, and 4) prevented the decline in learning abilities (P < 0.05). In conclusion, catechin treatment of ATX mice prevents cerebrovascular dysfunctions and the associated decline in learning capacities.     

Light deprivation-related changes of strategy selection in the radial arm maze

During the early postnatal age environmental signals underlie the development of sensory systems. The visual system is considered as an appropriate system to evaluate role of sensory experience in postnatal development of sensory systems. This study was made to assess the effect of visual deprivation on strategy of arm selection in navigation of radial arm maze. Six-week-old light- (LR, control) and dark-reared (DR) rats were trained for correct choices and adjacent arms tasks. Our results showed that both the LR and DR animals equally selected correct arms. In the adjacent arms task, however, the control group significantly outperformed the DR animals. While the LR males and females displayed some differences in performing the tasks, no sex dependency was found in the performance of the DR group. These findings indicate that the lack of visual experience is likely to influence the strategy selection as well as sex differences. Thus the difference in the performance of LR and DR animals seems to be due to the male rather than female behavior.     

'Return to home cage' as a reward for maze learning in young and old genetically heterogeneous mice

Recent studies have shown that 'return to home cage' can serve as a reward for maze learning in adult male mice. The present study examined whether the same reward is an effective motivator of learning in young and old mice and included females in the study design. We tested 25- and 65-d-old HS mice and 85- and 800-d-old B6D2F2 mice in a Lashley III maze. Return to home cage motivated maze acquisition in all groups. Compared with 65-d-old HS mice, 25-d-olds acquired the maze more slowly, took longer to achieve the test criterion, and showed increased latency to reach the goal box. There was no difference between 85- and 800-d-old B6D2F2 mice in rate of acquisition. This reward procedure may reduce the potentially confounding effects of deprivation or aversive stimuli on maze performance and may be suitable as a motivational procedure for a wide range of subject groups.     

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.     

Behavioral tactics of rats receiving unequally distributed reinforcement in a radial maze

Rats behaviour was studied in 12-arms radial maze with food reinforcement of different volumes presented only in 6 passages. Dynamics of changes is shown in the process of learning both in the preference of the passages with greater volume of reinforcement and in the number of errors, characterizing the working and referent memories. In the trained rats, their behaviour is determined by at least two behavioural tactics: visiting more remote passages and choice in the beginning of the test of more reinforced passages.     

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.     

An observational learning task using Barnes maze in rats

Observational learning, which modulates one’s own behavior by observing the adaptive behavior of others, is crucial for behaving efficiently in social communities. Although many behavioral experiments have reported observational learning in monkeys and humans, its neural mechanisms are still unknown. In order to conduct neuroscientific researches with recording neural activities, we developed an observational learning task for rats. We designed the task using Barnes circular maze and then tested whether rats (observers) could actually improve their learning by observing the behavior of other rats (models) that had already acquired the task. The result showed that the observer rats, which were located in a metal wire mesh cylinder at the center of the maze and allowed to observe model rats escaping to the goal in the maze, demonstrated significantly faster escape behavior than the model rats. Thus, the present study confirmed that rats can efficiently learn the behavioral task by observing the behavior of other rats; this shows that it is conceivable to elucidate the neural mechanisms of social interaction by analyzing neural activity in observer rats performing the observational learning task.     

Training of rats of the Wistar and Krushinskii-Molodkinaia lines in a radial maze

The experiments were conducted on rats of Wistar (W) and Krushinsky--Molodkina (KM) (with audiogenic epilepsy) lines in 12-rays radial-symmetrical labyrinth. The trained rats of W line made less erroneous (repeated) visits to the labyrinth corridors than the rats of KM line. The corridors repeatedly visited by the rats of W line were more frequently situated near the unvisited corridors. No definite sequence of corridors' visiting by the rats of both lines was observed; still there was a tendency to choose corridors the most remoted from each other. This tendency intensified in the process of training. This is considered as one of tactics of rats' behaviour, providing for adequate reactions in definite surrounding conditions.