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PubMed2002

Integration and representation in rats' serial pattern learning in the T-maze.

Rats were exposed to three-trial series consisting of reinforced (R) trials and one nonreinforced (N) trial in a fixed order, RRN and RNR (Experiments 1 and 2) or NRR and RRN (Experiment 3), on extended visually distinct runways in a T-maze. When initially presented with the same sequence on each series in a session (separate presentations) with the same runway on all trials within a series (Experiments 1 and 3), all the rats developed slower running speeds on N than on R trials. When a runway was sometimes changed between the first and next two trials during separate presentations training (Experiment 2) or both sequences were later intermixed within each session in each experiment, only rats exposed to each sequence on a specific runway maintained these serial running patterns. Rats displayed serial running patterns on a test RNN sequence similar to that on the RNR sequence (Experiment 2), as would be predicted by an intertrial association model of serial pattern learning (Capaldi & Molina, 1979), but responded on test RRR and NRN sequences (Experiment 3) as would be predicted by an ordinal-trial-tag/intratrial association model (Burns, Wiley, & Payne, 1986). Results from test series of free-choice trials in Experiments 1 and 2 failed to support a prediction of the intratrial association model that these rats would integrate RRN and RNR sequences. Rather than always selecting a baited runway on both the second and the third free-choice trials, the rats only selected a baited runway on the third trial on the basis of their choice on the second trial, as would be predicted by the intertrial association model. Only after experiencing all possible outcome sequences during forced-choice training in Experiment 3 did these rats predominantly select a baited runway on every free-choice trial.

Animals↗
PubMed1978

[Learning behavior of rats on the water maze (author's transl)].

The Learning behavior on a water maze was observed in Wistar-JCL rats which were 10 weeks of age at the beginning of tests. Each rat was given five swimming trials in a straightway on the first day, as well as daily five trials to escape from a water maze on the 2nd to 4th day of the tests. In the first trial of the straightway, the harmonic means of the swimming time were 12.0 and 17.4 seconds in the male and females, respectively. In each trial of the water maze, there were no significant differences between the female on the spent time and the number of errors. During the test days, the median of total of errors were 25.2 and 24.3 times in the male and female, respectively. Error response entered into a blind alley occurred beside the starting point more frequently than the goal.

Animals↗
PubMed1995

[Three simple maze tests employing mice housed in maze apparatuses].

This report deals with three different maze methods using spontaneous learning behavior. Forty-eight mice housed in an apparatus with a multiple maze mastered the maze task on the 5th day after the start of housing. Then they were divided into four groups, and two of the groups were treated with AF64A (3.5 nmol, i.c.v.) or trimethyltin (TMT, 3 mg/kg, p.o.), and the other two groups were treated with the vehicle as the respective control. Seven days after the treatment, their memory retrieval was tested. Subsequently, the same mice were housed in the apparatus with a T-maze. After the finish of the experiment using the T-maze, they were housed in the apparatus with an eight arm radial maze. The control groups mastered the T-maze task with a 3-sec delay on the 4th day after the start of housing and the radial maze task on the 10th day after the start of housing. Both the treatments lowered the performance in all maze tasks. These results show that the mice housed in the apparatus with maze learned to negotiate the maze spontaneously, and the apparatuses are useful for estimating memory in mice with little effort.

Animals↗
PubMed1996

Effects of triazolam and diazepam on learning and memory as assessed using a water maze.

One of the reported adverse side effects of the frequently prescribed benzodiazepines diazepam (Valium) and triazolam (Halcion) is an impairment of anterograde memory in humans. The experiments described in this article compared the effects of triazolam and diazepam on performance in a water maze task that is sensitive to drugs that affect learning and memory. The water maze utilized is a traditional type of maze with alleyways and door choices, unlike the Morris open water maze. Time required to find an out-of-the-water platform and errors committed during the swim are used as performance measures. Rats were tested on a previously learned maze configuration and on the acquisition of new maze configurations. Neither diazepam (0.25, 1.0, or 2.0 mg/kg) nor triazolam (0.05, 0.2, or 0.3 mg/kg) injected 30 min prior to testing on the previously learned maze affected swim time or errors committed. Administration of diazepam (0.5, 1.0, or 2.0 mg/kg, IP) prior to daily training on three different new maze configurations did not affect swim time, but did increase swim errors. Triazolam administered at 0.1, 0.2, or 0.3 mg/kg markedly impaired performance as assessed by either swim time or errors. There were no differences in performance of rats previously treated with triazolam, diazepam, or vehicle in learning another new maze after drug treatment was terminated. These data demonstrate that both diazepam and triazolam affect acquisition but not recall of maze configurations and support similar conclusions reached using other types of tasks in humans and animals.

Animals↗
PubMed2001

Long-term effects of low-level sarin inhalation exposure on the spatial memory of rats in a T-maze.

1. To study the influence of low-level sarin exposure on cognitive functions, male albino Wistar rats were exposed to three various low concentrations of sarin (LEVEL 1-3) for 60 minutes in the inhalation chamber. Testing of cognitive functions was carried out using the T-maze evaluating learning and spatial memory. The behavior of sarin-exposed rats in the T-maze was tested several times within five weeks following sarin inhalation exposure to look for any cognitive impairments. The alteration of cognition was evaluated by using a method studying memory elicitation in response to appetitive motivation in a multiple T-maze. 2. Statistically significant, short-term deficiency in the T-maze performance was observed in rats exposed to symptomatic (LEVEL 3) as well as clinically asymptomatic concentration (LEVEL 2) of sarin. The repeated exposure of rats to clinically asymptomatic dose of sarin (LEVEL 2R) did not change the effect of low-level sarin exposure on spatial memory compared to the single exposure to the same dose of sarin. 3. Thus, sarin is able to influence the cognitive functions (e.g. spatial memory) even at low doses that do not cause clinically manifested intoxication following the inhalation exposure. Nevetheless, the alteration of spatial memory lasts for a short time only, in contrast with the severe sarin poisoning.

Administration, Inhalation↗
PubMed2004

Effects of runway shift and stay rules on rats' serial pattern learning in the T-maze.

Rats received three-trial series on a T-maze consisting of extended visually distinct left-black and right-striped side runways. During the first phase of training, when allowed to select baited runways within these series, they predominantly alternated their choices. During the second phase, rats received forced-choice serial pattern training of series consisting of two rewarded (R) trials and one nonrewarded (N) trial in two fixed orders, RRN and RNR. In Experiment 1, the rats in the runway shift rule group always received the second R trial when forced down a runway opposite that on the preceding trial in the series and the N trial when forced down the same runway. The rats in the runway stay rule group always received the second R trial when forced down the same runway and the N trial when forced down the opposite runway. In Experiment 2, each rat was conditionally trained with both runway outcome rules as determined by the central alley lighting and the type of food in the side alleys. The rats took longer to reduce their running speed on the N trial within each sequence under the runway stay rule than under the runway shift rule. They also took longer to acquire serial pattern responding for the RNR than for the RRN series only under the runway stay rule condition. When subsequently reexposed to series of free-choice trials on the final phase, rats maintained spontaneous alternating choice patterns under the runway shift rule conditions but either seldom alternated their choices (Experiment 1) or greatly reduced choice alternations (Experiment 2) under the runway stay rule condition. We discussed these effects in terms of rats' natural foraging strategies and as a factor that interacts with other within- and between-series variables that affect serial pattern behavior.

Animals↗
PubMed1998

Effect of traumatic brain injury on mouse spatial and nonspatial learning in the Barnes circular maze.

Controlled cortical impact (CCI) is a relatively new model of traumatic brain injury in the mouse, which, in combination with behavioral and histological methods, has potential for elucidating underlying mechanisms of neurodegeneration using genetically altered animals. Previously, we have demonstrated impaired spatial learning in a water maze task following CCI injury at a moderate level. There are many difficulties associated with this task, however, such as stress, physical demand, and the multiple trials over days required for satisfactory training. As a potential alternative to the water maze, we adapted the Barnes circular maze to our mouse model and assessed spatial/nonspatial learning following injury. Mice were trained to locate a dark tunnel, hidden beneath one of 40 holes positioned around the perimeter of a large, flat, plastic disk, brightly illuminated by four overhead halogen lamps. Sham-operated animals rapidly acquired this task, exhibiting reduced latency to find the tunnel and a more efficient search strategy as compared with injured mice. This difference was not due to visuomotor deficits, as all mice performed equally well in a cued version of the same task. These results demonstrate spatial learning impairment following CCI injury in a task that offers an efficient alternative to the water maze.

Acute Disease↗
PubMed2004

Behavioral alterations induced by repeated testing in C57BL/6J and 129S2/Sv mice: implications for phenotyping screens.

The C57BL/6JOlaHsd and 129S2/SvHsd mice were tested in a battery designed for behavioral phenotyping of genetically modified mice. The study was performed in order to reveal the effect of training history on the behavior by comparison with the experimentally naive mice in the same tests. Significant strain differences were obtained in all experiments. Previous handling and testing reduced exploratory activity and emotionality significantly in the mice. The coordination ability was better and nociceptive sensitivity was increased in the trained mice. The contextual fear was reduced whereas the cued fear was enhanced in the experienced mice. The training history did not alter initial learning in the water maze. However, after reversal learning the naive mice displayed significant preference for both old and new platform locations, whereas the battery animals did not exhibit preference to the old location. The experienced mice appeared to be less active in the forced swimming test and exhibited decreased conditioned taste aversion. The influence of test history was strain-dependent in certain cases. Therefore, the experience has substantial consequences on the behavior, mainly by reducing exploratory activity, and the previous experience of the animals has always to be considered in the analysis of genetically modified mice.

Animals↗
PubMed2004

Role of a neuronal small non-messenger RNA: behavioural alterations in BC1 RNA-deleted mice.

BC1 RNA is a small non-messenger RNA common in dendritic microdomains of neurons in rodents. In order to investigate its possible role in learning and behaviour, we compared controls and knockout mice from three independent founder lines established from separate embryonic stem cells. Mutant mice were healthy with normal brain morphology and appeared to have no neurological deficits. A series of tests for exploration and spatial memory was carried out in three different laboratories. The tests were chosen as to ensure that different aspects of spatial memory and exploration could be separated and that possible effects of confounding variables could be minimised. Exploration was studied in a barrier test, in an open-field test, and in an elevated plus-maze test. Spatial memory was investigated in a Barnes maze and in a Morris water maze (memory for a single location), in a multiple T-maze and in a complex alley maze (route learning), and in a radial maze (working memory). In addition to these laboratory tasks, exploratory behaviour and spatial memory were assessed under semi-naturalistic conditions in a large outdoor pen. The combined results indicate that BC1 RNA-deficient animals show behavioural changes best interpreted in terms of reduced exploration and increased anxiety. In contrast, spatial memory was not affected. In the outdoor pen, the survival rates of BC1-depleted mice were lower than in controls. Thus, we conclude that the neuron-specific non-messenger BC1 RNA contributes to the aptive modulation of behaviour.

Analysis of Variance↗
PubMed1998

Late behavioural and neuropathological effects of local brain irradiation in the rat.

The delayed consequences of radiation damage on learning and memory in rats were assessed over a period of 44 weeks, commencing 26 weeks after local irradiation of the brain with single doses of X-rays. Doses were set at levels known to produce vascular changes alone (20 Gy) or vascular changes followed by necrosis (25 Gy). Following T-maze training, 29 weeks after irradiation, irradiated and sham control groups performed equally well on the forced choice alternation task. When tested 35 weeks after irradiation, treated rats achieved a much lower percentage of correct choices than controls in T-maze alternation, with no difference between the two irradiated groups. At 38-40 weeks after irradiation, rats receiving both doses showed marked deficits in water maze place learning compared with age-matched controls; performance was more adversely affected by the higher dose. The extent of impairment was equivalent in the two groups of rats irradiated with 25 Gy, those trained or not previously trained in the T-maze, suggesting that water maze acquisition deficits were not influenced by prior experience in a different spatial task. In contrast to water maze acquisition, rats irradiated with 20 Gy showed no deficits in working memory assessed in the water maze 44 weeks after irradiation, whereas rats receiving 25 Gy showed substantial impairment. Rats receiving 25 Gy irradiation showed marked necrosis of the fimbria and degeneration of the corpus callosum, damage to the callosum occurring in animals examined histologically 46 weeks after irradiation, but in only a third of the animals examined at 41 weeks. However, there was no evidence of white matter necrosis in rats irradiated with 20 Gy, examined 46 weeks after irradiation. These findings demonstrated that local cranial irradiation with single doses of 20 and 25 Gy of X-rays produced delayed impairment of spatial learning and working memory in the rat. The extent of these deficits appears to be task- and dose-related, since rats treated with 25 Gy showed marked impairments in all measures, whereas rats treated with the lower dose showed less impairment in water maze learning and no deficits water maze working memory, despite significant disruption of working memory in the T-maze. The findings further suggest that although high dose irradiation-induced white matter necrosis is associated with substantial impairment, cognitive deficits may also be detected after a lower dose, not associated with the development of necrosis.

Animals↗
PubMed1994

I.c.v. infusions of ACPD(1S,3R) attenuate learning in a Morris water maze paradigm.

The functional role of metabotropic glutamate receptors is beginning to be understood. Cognitive effects of metabotropic receptor activation were examined in the present study in a Morris water maze following intraventricular (i.c.v.) infusions of ACPD(1S,3R). I.c.v. infusions of ACPD substantially increased the amount of time animals took to find a hidden platform in a water maze. Current results demonstrate that subtoxic doses of ACPD can produce in vivo effects with functional significance. Spatial learning abilities are impaired following activation of metabotropic receptors with ACPD(1S,3R). Negative implications are provided for the use of cognitive enhancing compounds that stimulate metabotropic glutamate receptors.

Analysis of Variance↗
PubMed2001

The influence of low-level sarin inhalation exposure on spatial memory in rats.

To study the influence of low-level sarin exposure on cognitive functions, the rats were exposed to three various low concentrations of sarin (Levels 1-3) for 60 min in the inhalation chamber. In addition, one group of rats was exposed to Level 2 of sarin repeatedly. Testing of cognitive functions was carried out using the Y-maze evaluating learning and spatial memory. The correct averse behavior of sarin-exposed rats in the Y-maze was tested several times within 6 weeks following sarin inhalation exposure to look for any cognitive impairments. The results were compared to the Y-maze performance of control rats exposed to pure air instead of sarin. While a subtle and short-term deficiency in the Y-maze performance was observed in rats exposed to the Levels 1 and 2 of sarin, the exposure to the Level 3 of sarin caused a significant decrease in the Y-maze performance for a relatively long time. Similar sarin-induced spatial memory impairments were demonstrated in rats exposed repeatedly to the Level 2. A decrease in the Y-maze performance was observed until the end of the third week following the last exposure to sarin. Thus, our findings confirm that both nonconvulsive symptomatic and clinically asymptomatic concentrations of sarin can cause relatively long-term memory impairments in sarin-poisoned rats when the rats are exposed to clinically asymptomatic sarin concentration repeatedly.

Administration, Inhalation↗
PubMed2002

The impairment of spatial memory following low-level sarin inhalation exposure and antidotal treatment in rats.

1. To study the influence of antidotes on low-level sarin-induced impairment of cognitive functions, the rats were exposed to three various low concentrations of sarin (LEVEL 1-3) for 60 minutes in the inhalation chamber. In addition, one group of rats was exposed to LEVEL 2 of sarin repeatedly. 2. Testing of cognitive functions was carried out using the Y-maze evaluating learning and spatial memory. The correct averse behavior of sarin-exposed rats in the Y-maze was tested several times within four weeks following sarin inhalation exposure and antidotal treatment to look for any cognitive impairments. 3. The results were compared to the Y-maze performance of sarin-exposed rats without antidotal treatment and control rats exposed to pure air instead of sarin with or without antidotal treatment. While antidotal treatment was able to eliminate a short-term deficiency in the Y-maze performance in rats exposed to the LEVEL 1 of sarin, a significant decrease in the Y-maze performance in rats exposed to sarin at the LEVEL 2 and 3 was only shortened. Sarin-induced spatial memory impairments in rats exposed repeatedly to sarin at the LEVEL 2 was also shortened when rats were treated following each sarin inhalation exposure. 4. The findings confirm that antidotes currently used for nerve agent poisonings are beneficial for the treatment of rats singly or repeatedly exposed to non-convulsive symptomatic or even clinically asymptomatic concentrations of sarin.

Administration, Inhalation↗
PubMed1995

Entorhinal-perirhinal lesions impair performance of rats on two versions of place learning in the Morris water maze.

The effects of entorhinal-perirhinal lesions in rats were studied with 2 versions of a place learning task in the Morris water maze. These lesions impaired performance on a multiple-trial task (3 days of 6 trials and a probe trial). This assessment was followed by a task in which rats were repeatedly trained to find novel locations with a variable delay (30 s or 5 min) imposed between each sample trial and retention test. Entorhinal-perirhinal damage produced a delay-dependent deficit in spatial memory: Rats with lesions were impaired at the 5-min delay relative to the control group and to their own performance at 30 s. These findings are discussed in relationship to memory impairment after entorhinal damage and spatial learning deficits observed after hippocampal damage.

Animals↗
PubMed2006

Restoring theta-like rhythmicity in rats restores initial learning in the Morris water maze.

Neural activity often becomes rhythmic during mental processing. But there has been no direct proof that rhythmicity, per se, is important for mental function. We assessed this issue in relation to the contribution of hippocampal theta-frequency rhythmicity to learning in the Morris water maze by blocking theta (and other septal inputs to the hippocampus) and then using electrical stimulation to restore rhythmicity. We injected tetracaine into the medial septal area, and so blocked septal input to the hippocampus in rats throughout 16 consecutive trials in a Morris water maze. Rats with no hippocampal theta also showed no initial learning in the maze. Theta rhythmicity in the supramammillary area remained after septal blockade, and we used this to trigger electrical stimulation of the fornix superior. This substantially restored hippocampal theta-like rhythmicity throughout training at a normal frequency but with abnormal wave forms. This treatment applied throughout training substantially restored initial learning. Fixed frequency (7.7 Hz) stimulation produced rhythmic activity and a brief improvement in learning. Irregular stimulation with an average frequency of 7.7 Hz produced little rhythmicity and little improvement in learning. These results demonstrate that brain rhythmicity, per se, can be important for mental processing even when the detailed information originally carried by neurons is lost and when the reinstated pattern of population firing is not normal. The results suggest that the precise frequency of rhythmicity may be important for hippocampal function. Functional rhythmicity needs, therefore, to be included in neural models of cognitive processing. The success of our procedure also suggests that simple alterations of rhythmicity could be used to ameliorate deficits in learning and memory. (c) 2006 Wiley-Liss, Inc.

Analysis of Variance↗