Differential Effects of Global Ischemia on Delayed Matching- and Non-Matching-to-Position Tasks in the Water Maze and Skinner Box

In order to assess effects of global ischemia in tasks of spatial learning and working memory, male Wistar rats were subjected to four vessel occlusion (4 VO) for periods of 5, 10, and 20 min and compared with sham-operated controls over four test phases, from 6 to 54 weeks after surgery. Rats were assessed on acquisition in the water maze, a task that is sensitive to ischemic impairments, before testing in Skinner box and water maze working memory tasks, which both require the short-term storage of information, but make different demands on spatial information processing. Phases 1 and 3 assessed spatial learning in a standard water maze procedure (12 and 10 training days, 2 trials/day with a 10-min intertrial interval: ITI). Phase 2 involved training and testing in delayed non-matching-to-position task in the Skinner box, with delays of 2–10 s between the information and choice stages. Phase 4 examined working memory in a water maze delayed matching-to-position task with 4 trials/day, an ITI of 30 s, and a novel platform position on each day. Ischemic rats showed duration-related impairments in water maze acquisition and working memory, but not in the less spatially demanding Skinner box task. Since water maze acquisition deficits were seen both before and after testing in the Skinner box the lack of effect cannot be attributed to time or to prior training. Ischemic deficits were more marked in Phase 3 than in Phase 1 of acquisition, suggesting that impairment may be progressive. Histological assessment showed that cell loss was largely confined to the hippocampal CA1 field and was linearly related to duration of occlusion. At the maximal level of loss (5.7 mm before the interaural line) the 20-min group showed 90% loss, the 10-min group 60% loss, and the 5-min group, which did not differ from controls, less than 10% loss. Only the 20-min group showed significant damage beyond the CA1 field, ranging from 30–40% loss in the CA3 field to 5% loss in one striatal area. No cortical damage was seen. The extent of CA1 cell loss correlated modestly with water maze acquisition (Phase 3) and working memory scores, but not with trials to criterion in the Skinner box task. There were significant correlations between different measures both within and between water maze tasks, but not Skinner box tasks, suggesting that the two types of procedure engaged different cognitive processes. The results indicate that the intrahippocampal damage induced by 4 VO impaired tasks which required processing of allocentric spatial information, but did not impair the storage of limited spatial information in working memory.     

东莨菪碱对大鼠空间参考记忆和工作记忆的不同影响

观察东莨菪碱对空间参考记忆和空间工作记忆的编码、保持和提取过程的作用。应用Morris水迷宫实验测定大鼠的空间参考记忆和空间工作记忆,分别在训练的不同阶段腹腔注射东莨菪碱（1mg/kg）和相同容量的生理盐水,比较各东莨菪碱组和生理盐水组之间游泳潜伏期、路径长度、轨迹和游泳速度的差异。结果发现：与注射生理盐水相比,在训练前和探测实验前注射东莨菪碱的大鼠在探测实验中对目标象限不表现出空间偏爱,说明东莨菪碱干扰参考记忆的信息编码和提取过程;而在训练结束后注射东莨菪碱的大鼠探测实验的结果与生理盐水组相比没有显著差异,说明东莨菪碱对参考记忆的保持过程没有影响。在工作记忆实验中,无论第一次测试前、第一次测试后和第2次测试前注射东莨菪碱,均造成大鼠游泳潜伏期延长,说明东莨菪碱干扰工作记忆的编码、保持和提取过程。研究提示M受体在空间工作记忆和参考记忆中发挥不同作用     

Chronic propranolol induces deficits in retention but not acquisition performance in the water maze in mice

Agents that alter adrenergic receptors, such as "beta-blockers," also alter memory storage. However, reports suggest that beta-adrenergic receptor antagonists, such as propranolol, have conflicting behavioral effects with acute vs chronic dosing. This study was designed to evaluate the effects of chronic propranolol on retention for a spatial learning task. Adult male ICR mice were given daily injections of propranolol (2, 4, 8, or 12 mg/kg ip) or 0. 9% NaCl for 15 days prior to, and during, trials in a Morris water maze. Mice received five massed acquisition (escape) trials in each of three daily sessions, followed by a single 60-s probe trial on the fourth day. The location of the submerged platform was constant for each animal over acquisition trials, but varied across animals; starting position varied across trials. A 5 (dose) x 3 (trial blocks) mixed factorial ANOVA for escape time yielded a significant trial blocks effect only (p <.001), showing performance improving over sessions. Time spent in the target quadrant on the probe trial was shorter under all doses of propranolol when compared to vehicle group (all p <.001), indicating poorer retention of prior platform location. This effect, however, was not dose-related. Swim speed was not significantly affected by propranolol. These data demonstrate that chronic dosing with propranolol can impair retention of spatial learning, which cannot be attributed to reduced arousal or motor function.     

Effects of ketamine on tunnel maze and water maze performance in the rat

The NMDA receptor, which has been implicated in memory formation, is noncompetitively blocked by ketamine. The present study examines the effect of ketamine (0, 3, 6, 12, and 25 mg/kg body wt; ip) on tunnel maze and water maze performance in Wistar rats. In the hexagonal tunnel maze (HTM) high doses of ketamine (12 and 25 mg/kg) decreased locomotor activity. Moreover, ketamine induced perimeter walking (6, 12, and 25 mg/kg) and attenuated exploratory efficiency (25 mg/kg). When the HTM was converted into a modified six-arm radial maze, ketamine impaired short-term but not long-term memory. In the Morris water maze, rats injected with ketamine (12 and 25 mg/kg) acquired a spatial navigation task more slowly than controls. When the escape platform was removed, the drug-treated rats did not preferentially search for it in the area where the platform had been during the acquisition phase. However, when the escape platform was visible, no differences in the performance of ketamine-treated and control rats could be found. In summary, ketamine seems to attenuate some but not all forms of learning in the tunnel maze and it impairs the acquisition of a spatial navigation task.     

A room with a view and a polarizing cue: individual differences in the stimulus control of place navigation and passive latent learning in the water maze

We investigated individual differences in the stimulus control of navigational behavior in the water maze by comparing measures of place learning in one environment to measures of latent learning (via passive placement on the goal platform) in a novel environment. In the first experiment, 12 rats were trained to find a slightly submerged hidden platform at a fixed location in room A for 10 days (4 trials/day). Fast and slow place learners were identified by their mean escape latency and cumulative distance to the goal during acquisition. The same animals were then given a 2-min passive placement on the submerged platform in room B. Latent learning was assessed by the animal's escape latency on a single swim trial immediately following the placement in room B. The results showed that the good latent learners in room B were not necessarily the fast place learners in room A. This weak correlation may be related to the fact that some rats swam near the area in room B that corresponded to the former goal location in room A relative to a common polarizing cue (i.e., the door/entrance to both rooms). When the view of the door was blocked in a second experiment a significant positive correlation between place acquisition and the latent learning test was obtained, although escape performance following passive placement was not improved. These findings suggest that while place navigation and latent learning via passive placement may involve some common cognitive-spatial function, other associative (S-S and/or S-R) processes that occur during place navigation/active movement may be required for animals to exhibit truly accurate navigational behavior characteristic of asymptotic escape performance in the water maze. Additional implications for neurobiological studies using a procedural pretraining design are discussed.     

Applying an exemplar model to the serial reaction-time task: Anticipating from experience

We present a serial reaction time (SRT) task in which participants identified the location of a target by pressing a key mapped to the location. The location of successive targets was determined by the rules of a grammar, and we varied the redundancy of the grammar. Increasing both practice and the redundancy of the grammar reduced response time, but the participants were unable to describe the grammar. Such results are usually discussed as examples of implicit learning. Instead, we treat performance in terms of retrieval from a multitrace memory. In our account, after each trial, participants store a trace comprising the current stimulus, the response associated with it, and the context provided by the immediately preceding response. When a target is presented, it is used as a prompt to retrieve the response mapped to it. As participants practise the task, the redundancy of the series helps point to the correct response and, thereby, speeds retrieval of the response. The model captured performance in the experiment and in classic SRT studies from the literature. Its success shows that the SRT task can be understood in terms of retrieval from memory without implying implicit learning.     

The effects of a target–stimulus reminder on performance in a novel object recognition task

The effects of original training-stimulus pre-test reminders were examined in a novel object recognition (NOR) task. NOR is a task that examines memory for complex stimuli, and is driven by the rats’ tendency to spend significantly more time exploring novel objects over those previously experienced. In this task, a delay is imposed between a training experience during which the animal is allowed to investigate a set of identical objects, and a later test exposure where the animal encounters one of the original objects and a novel object with which it has had no previous experience. Experiment 1 demonstrated that performance at 24 h is significantly worse than at an immediate delay (1 min). In the second experiment, it was demonstrated that neither a 10-s nor a 30-s reminder treatment, in the absence of training, resulted in a level of preference for novelty, a measure of memory for the original object, that was significantly greater than chance. Experiment 3 illustrated significant performance effects of a 30-s training stimulus reminder administered 15 min prior to test with a 24-h retention interval. The final experiment illustrated that the additional 30-s of object exposure is effective in enhancing performance only if it occurs shortly prior to test. Animals receiving the additional 30-s immediately following training did not experience such beneficial effects. It was concluded, based upon these results, that pre-test training-stimulus reminders in this task produce effects similar to those seen in more traditional tasks of learning and memory.     

Estrogen replacement in ovariectomized rats affects strategy selection in the Morris water maze

While estrogen enhances performance on some tasks of learning and memory, it has impairing or no effects on others. It has been proposed that estrogen differentially affects performance on various tasks of learning and memory by influencing the strategy used to solve a task. The goal of the present study was to determine if estrogen would influence strategy selection in the Morris water maze. Long-Evans rats were ovariectomized and implanted with Silastic capsules containing 25% estradiol diluted in cholesterol or 100% cholesterol. Rats were trained in a water maze task in which multiple strategies were available for use to locate a hidden escape platform that was moved to a new location for each set of four daily trials. During 10 days of acquisition trials, a visible floating landmark was always located in a static position relative to the hidden escape platform. Additionally, fixed extramaze cues visible to the animals surrounded the maze. Following acquisition, 2 days of probe trials were conducted in which the static landmark was removed. Estrogen replacement in ovariectomized rats resulted in impaired performance across 10 days of acquisition. Additionally, while removal of the visible landmark during the probe trials had no effect on the performance of the females receiving estrogen, it significantly disrupted performance of females receiving cholesterol treatment. These results indicate that estrogen replacement in ovariectomized rats biases an animal against using a landmark or static cue to aid in the location of a hidden escape platform in the water maze.     

Vitamins E and C pretreatment prevents ovariectomy-induced memory deficits in water maze

We investigated whether the pretreatment with vitamins E (alpha-tocopherol) and C (ascorbic acid) would act on ovariectomy-induced memory deficits in Morris water maze tasks. Adult female Wistar rats were divided into three groups: (1) naive (control), (2) sham (submitted to surgery without removal of ovaries) and (3) ovariectomized. Thirty days after surgery, they were trained in the Morris water maze in order to verify ovariectomy effects both on reference and working memory tasks. Results show that ovariectomized rats presented impairment in spatial navigation in the acquisition phase, as well as in the time spent in target quadrant and in the latency to cross over the location of the platform in test session, when compared to naive and sham groups (controls), in the reference memory task. Ovariectomy did not affect performance in the working memory task. Confirming our hypothesis, ovariectomized rats pretreated for 30 days with vitamins E and C had those impairments prevented. We conclude that ovariectomy significantly impairs spatial reference learning/memory and that pretreatment with vitamins E and C prevents such effect. Assuming this experimental memory impairment might mimic, at least in part, the cognitive deficit sometimes present in the human condition of lack of reproductive hormones, our findings lend support to a novel therapeutic strategy, based on vitamins E and C, to cognitive impairments in post-menopausal women.     

Cue effects on memory for location when navigating spatial displays

Participants maneuvered a rat image through a circular region on the computer screen to find a hidden target platform, blending aspects of two well-known spatial tasks. Like the Morris water maze task, participants first experienced a series of learning trials before having to navigate to the hidden target platform from different locations and orientations. Like the dot-location task, they determined the location of a position within a two-dimensional circular region. This procedure provided a way to examine how the number of surrounding cues (1, 2, or 3) affects the memory for spatial location in navigation. Memory performance was better when there were more cues and when targets were close to cues, consistent with the idea that cues bolster fine-grain memory, especially in proximal regions. Early and late measures of bias in memory reflected biases in a direction toward the nearest cue, implicating a cue-based category structure of the navigational space. Collectively, results suggest cue-based spatial memory representations that have been inferred from the dot-location task generalize to a navigation task within a simple, computer-based environment, as demonstrated by the good fits of the spatial model developed for the dot-location task ( Fitting, Wedell, & Allen, 2005, 2007 ).     

Age-related impairments of new memories reflect failures of learning,not retention

Learning impairments and the instability of memory are defining characteristics of cognitive aging. However, it is unclear if deficits in the expression of new memories reflect an accelerated decay of the target memory or a consequence of inefficient learning. Here, aged mice (19–21-mo old) exhibited acquisition deficits (relative to 3–5-mo old mice) on three learning tasks, although these deficits were overcome with additional training. When tested after a 30-d retention interval, the performance of aged animals was impaired if initial learning had been incomplete. However, if trained to equivalent levels of competence, aged animals exhibited no retention deficits relative to their young counterparts. These results suggest that age-related “memory” impairments can be overcome through a more effective learning regimen.Aging is associated with broad deficits in the acquisition of new knowledge (Matzel et al. 2008; see, for review, Gallagher and Rapp 1997; Rosenzweig and Barnes 2003), as well as impairments in the retrieval of both old and newly acquired information. While it is clear that old memories (i.e., ones obtained prior to age-related cognitive declines) do in fact become less stable with age (Gallagher 1997), it is less clear whether newly attained memories are inherently less stable in aged animals, or whether age-related memory deficits reflect a secondary consequence of inefficient learning.The majority of published data regarding cognitive aging describes impairments of animals'' learning abilities (Gage and Dunnett 1984; Markowska et al. 1994; Meliska et al. 1997; Nalbantoglu et al. 1997; Vogel et al. 2002; Matzel et al. 2008), although a smaller percentage of these studies also report animals'' performances after long retention intervals. Of those studies that report retention deficits, in most of those studies the initial learning upon which the long-term memory was based was impaired relative to young animals (e.g., Barnes and McNaughton 1985; Kinney et al. 2001a,b; Gould and Feiro 2005). Interestingly, in those few studies in which initial learning was equated across young and old animals, including studies of spatial water maze performance and appetitive instrumental responding, no retention deficits were observed, even after retention intervals as long as 21 d (Soffie and Lejeune 1991; Martinez-Serrano et al. 1996; Port et al. 1996).Although suggestive, the above experiments were not systematically designed to assess the stability of memory in aged animals as a function of the level of initial learning. In the present study, young (3–5 mo) and old (19–21 mo) male Balb/C mice were trained in three learning tasks (a spatial water maze, an egocentric Lashley III maze, and a three-choice odor discrimination). When trained to pre-asymptotic levels, aged animals exhibited both learning and retention deficits (assessed 30 d after initial training). However, when aged animals were trained to levels of competence comparable to their young counterparts, both young and old animals exhibited statistically indistinguishable levels of retention.Sixty Balb/C mice arrived in our laboratory at 2.5 mo (n = 30) or 18.5 mo (n = 30) of age. Each age category was divided into two groups of 15, one of which would receive subasymptotic training on each of the three learning tasks, and one of which would receive extended training on those tasks. Two aged mice became ill during the course of testing and were excluded from all analyses. Young mice ranged from 19.8 to 29.1 g, and aged mice from 26.2 to 37.3 g. Maintenance, food deprivation, and training conditions were as previously described (Matzel et al. 2006, 2003). Behavioral testing of young and aged mice was concluded at ∼5 and 21 mo of age, respectively.All animals were tested in three independent learning tasks. Briefly, the spatial water maze encourages mice to integrate spatial information to efficiently escape from a pool of water. In odor discrimination, animals must use a target odor (from a group of three odors) to guide their search for food. In the Lashley III maze, animals learn an egocentric sequence of turns to obtain a food reinforcer. Training on each task required 2–10 d (depending on the task and the level of training), and animals received four days of rest between tasks. A retention test was administered 30 d after the last training trial of each task.A Lashley III maze was constructed from black Plexiglas. A 3-cm-diameter white disk was located in the center of the goal box, and a 45 mg Bio-Serv food pellet (dustless rodent grain) was placed at the center of the disk and served as the reinforcer. Food-deprived animals received a day of acclimation to the maze, followed by either one or two days of training (four trials/day). On the day prior to the acclimation, animals received three Bio-Serv pellets in their home cage (thus mitigating any neophobia to the food on subsequent exposures). On the acclimation day, each mouse was confined in each of the first three alleys of the maze for 4 min, and in the final alley (containing the goal box) for 6 min. On this acclimation day, three Bio-Serv pellets were placed in the goal box. On the subsequent training day(s), each animal was placed in the start box and allowed to freely navigate the maze, during which time the number of errors to reach the goal box were recorded. (An error was constituted by a turn in the wrong direction or a retracing of a previously completed path.) Upon consuming the food pellet, the animal was returned to its home cage for a 25-min intertrial interval (ITI). All animals completed four trials during the first training day. Half of those animals then received an additional four training trials on the following day. Twenty-nine days after the last training trial, all animals received three Bio-Serv pellets in their home cages, and on the subsequent day were again tested in the maze.For the water maze, a round pool (140 cm diameter, 56 cm deep) was filled to within 20 cm of the top with water that was clouded with a water soluble black paint. A hidden 14-cm-diameter black platform was located in a fixed position 1 cm below the surface of the water. The pool was enclosed by a ceiling high black curtain on which five different light patterns (which served as spatial cues) were fixed at various positions. These light cues provided the only illumination of the maze, which was 60 Lux at the water''s surface.On the day prior to training, each animal was confined for 360 sec to the platform by a clear Plexiglas cylinder that fits around the platform. For either one or two training days (six trials Day 1, five trials Day 2), the animals were started from one of three positions, such that no consecutive trials started from the same position. After locating the platform or swimming for 90 sec, the animals were left or placed on the platform for 10 sec, after which they were placed in a holding box (for 12 min) before the start of the next trial. After the sixth or 11th training trial, animals were returned to their home cages for 3 h, and were then administered a 30-sec “probe” test in which the escape platform was removed from the maze and the time spent searching in the target quadrant was recorded. One hour later each animal received an additional training trial (intended to re-establish the search strategy employed by the animal prior to the probe test). Animals were then returned to their home cages, where a 30-d retention interval began.In odor discrimination, mice navigate through a field using unique odors to guide them. The animals learn to choose the food cup that contains the target smell when given three choices. The food cup locations are rearranged on each trial, but the accessible food is always marked by the same target odor (in this case mint). The chamber consisted of a black Plexiglas 60-cm-square field with 30-cm-high walls, which was located in a dimly lit room with high ventilation. A food cup was located in three corners. The target cup had accessible food (30 mg of chocolate puffed rice), while the remaining cups contained food that could not be accessed. A cotton tipped swab (2-cm long) was loaded with 25 μL of lemon-, mint- (the target odor), or almond-flavored extract and extended vertically from the back corner of each cup.Each animal had one day of acclimation and one day of training (consisting of four training trials). (In this task, both young and old animals reached asymptotic levels of performance [near errorless] within four training trials.) On Day 1 (adaptation), each mouse was placed in the box for 20 min with no food cups present. On the subsequent training day, a food cup was placed in three corners of the field, but only the cup associated with the mint odor contained accessible food. Each animal received four trials in which they were placed in the corner of the training chamber that did not contain a food cup. A trial continued until the animal obtained the food from the target location, at which time the animal was returned to its home cage to begin a 20 min ITI. At the end of each trial the food cups were rearranged, but mint always remained as the target odor. For each trial, the number of errors (contact with or sniffing within 2 cm of an incorrect food cup) was recorded. After the fourth training trial, the animal was returned to its home cage for a 30-d retention interval. On the 29th retention day, all animals received three pieces of chocolate flavored rice in their home cages, and on the subsequent day were again tested as in original training.     

Intra-amygdala anxiogenic drug infusion prior to retrieval biases rats towards the use of habit memory

In a dual-solution plus-maze task that can be acquired using either hippocampus-dependent "cognitive/place" learning or dorsal striatal-dependent "habit/response" learning, pre-acquisition peripheral or intra-basolateral amygdala (BLA) injections of anxiogenic drugs result in the predominant use of response learning. The present experiments examined the effect of anxiogenic drug treatment on the relative use of multiple memory systems when administered prior to memory retrieval. Adult male Long-Evans rats were trained for two days (6 trials/day, 30s ITI) in a dual-solution plus-maze task to swim from the same start point (south) to an escape platform that was located in a consistent goal arm (west). On day three, prior to a memory retrieval probe trial from a novel start point (north), rats received a peripheral (0.03, 0.1 or 0.3 mg/kg), or intra-BLA (0.1 microg/0.5 microl) injection of the anxiogenic alpha(2)-adrenoreceptor antagonist RS 79948-197, or saline. Relative to saline controls, rats receiving either peripheral or intra-BLA infusions of RS 79948-197 predominantly displayed response learning on the probe trial. In an additional experiment peripheral (0.1 mg/kg) or intra-BLA (0.1 microg) drug injections administered prior to both acquisition and retrieval also resulted in the predominant use of response learning. The findings indicate that (1) similar to acquisition, peripheral injection of an anxiogenic drug prior to memory retrieval biases rats towards the use of habit/response memory, (2) intra-BLA infusions of an anxiogenic drug is sufficient to produce this modulatory effect of emotional state on memory retrieval, and (3) state-dependency does not appear to play a role in the effects of anxiogenic drug treatment on multiple memory system use. The findings may have implications for understanding the interaction between brain function, emotion, and the relative use of multiple memory systems in human psychopathology.     

An assessment of response, direction and place learning by rats in a water T-maze

Behavioral data suggest that distinguishable orientations may be necessary for place learning even when distal cues define different start points in the room and a unique goal location. We examined whether changes in orientation are also important in place learning and navigation in a water T-maze. In Experiment 1, rats were trained to locate a hidden platform and given a no-platform probe trial after 16 and 64 trials with the maze moved to a new position. Direction and response strategies were more prevalent than a place strategy. In Experiment 2, acquisition of place, response and direction strategies was assessed in a water T-maze that was moved between two locations during training. Rats were impaired on the place task when the maze was translated (moved to the L or R) but were successful when the maze was rotated across trials. These data are consistent with findings from appetitive tasks.     

Acute predator stress impairs the consolidation and retrieval of hippocampus-dependent memory in male and female rats

We have studied the effects of an acute predator stress experience on spatial learning and memory in adult male and female Sprague-Dawley rats. All rats were trained to learn the location of a hidden escape platform in the radial-arm water maze (RAWM), a hippocampus-dependent spatial memory task. In the control (non-stress) condition, female rats were superior to the males in the accuracy and consistency of their spatial memory performance tested over multiple days of training. In the stress condition, rats were exposed to the cat for 30 min immediately before or after learning, or before the 24-h memory test. Predator stress dramatically increased corticosterone levels in males and females, with females exhibiting greater baseline and stress-evoked responses than males. Despite these sex differences in the overall magnitudes of corticosterone levels, there were significant sex-independent correlations involving basal and stress-evoked corticosterone levels, and memory performance. Most importantly, predator stress impaired short-term memory, as well as processes involved in memory consolidation and retrieval, in male and female rats. Overall, we have found that an intense, ethologically relevant stressor produced a largely equivalent impairment of memory in male and female rats, and sex-independent corticosterone-memory correlations. These findings may provide insight into commonalities in how traumatic stress affects the brain and memory in men and women.     

Hamsters' (Mesocricetus auratus) memory in a radial maze analog: the role of spatial versus olfactory cues

The golden hamster's (Mesocricetus auratus) performance on radial maze tasks has not been studied a lot. Here we report the results of a spatial memory task that involved eight food stations equidistant from the center of a circular platform. Each of six male hamsters depleted the food stations along successive choices. After each choice and a 5-s retention delay, the hamster was brought back to the center of the platform for the next choice opportunity. When only one baited station was left, the platform was rotated to evaluate whether olfactory traces guided hamsters' choices. Results showed that despite the retention delay hamsters performed above chance in searching for food. The choice distributions observed during the rotation probes were consistent with spatial memory and could be explained without assuming guidance by olfactory cues. The radial maze analog we devised could be useful in furthering the study of spatial memory in hamsters.     

Damage to the retrosplenial cortex produces specific impairments in spatial working memory

Mounting evidence indicates that the retrosplenial cortex (RSP) has a critical role in spatial navigation. The goal of the present study was to characterize the specific nature of spatial memory deficits that are observed following damage to RSP. Rats with RSP lesions or sham lesions were first trained in a working memory task using an 8-arm radial arm maze. Rats were allowed 5 min to visit each arm and retrieve food pellets and a 5-s delay was imposed between arm choices. Consistent with previous research, rats with RSP damage committed more errors than controls. In particular, RSP-lesioned rats committed more errors of omission (failing to visit an arm of the maze), but there were no lesion effects on errors of commission (revisiting an arm). Neither group of rats exhibited a turn bias (i.e., always turning a certain direction when choosing an arm). At the end of the training phase of the experiment, both groups had reached asymptote and committed very few errors. In the subsequent test phase, a longer delay (30-s) was imposed during some sessions. Both control and RSP-lesioned rats continued to make few errors during sessions with the standard 5-s delay, but RSP-lesioned rats were impaired at the 30-s delay and committed more errors of commission, consistent with an increase in taxing spatial working memory.     

Norepinephrine infused into the basolateral amygdala posttraining enhances retention in a spatial water maze task

Recent evidence indicates that the amygdala plays a role in modulating memory processes in other brain regions. For example, posttraining intra-amygdala infusions of amphetamine enhanced memory in both spatial and cued training water maze tasks; these tasks are known to depend on the integrity of the hippocampus and caudate nucleus, respectively. To determine whether this modulation is dependent on noradrenergic activation within a subregion of the amygdala (the basolateral nucleus), the present study examined the effects of posttraining microinfusions (0.2 microl) of norepinephrine or propranolol into the basolateral amygdala immediately following training in a spatial version of the water maze task. Rats received a four-trial training session on each of 2 consecutive days. On the third day, rats were given a 60-s probe test in the absence of a platform. Retention latencies obtained on the second training day revealed that norepinephrine dose-dependently enhanced retention for the location of the hidden platform. In contrast, propranolol significantly impaired retention. Probe trial analysis revealed that rats treated with 0.25 microg norepinephrine demonstrated a selective spatial bias for the training platform location relative to all other groups. These findings are consistent with others and support the view that the basolateral amygdala has a role in modulating memory storage by interacting with other brain regions.     

Acute exposure to a 50 Hz magnetic field impairs consolidation of spatial memory in rats

This study was planned to evaluate the effect of an exposure to magnetic fields on consolidation and retrieval of hippocampus dependent spatial memory using a water maze. In Experiments 1 and 2, rats were trained in a hidden version (spatial) of water maze task with two blocks of four trials. The retention of spatial memory was evaluated 48 h later. Exposure to a 50 Hz 8 mT, but not 2 mT magnetic fields for 20 min immediately after training impaired retention performance. The same time exposure shortly before retention testing had no effect. In Experiment 3, rats were trained in a cued version of water maze with two blocks of four trials. Exposure to magnetic field at 8 mT for 20 min immediately after training did not impair retention performance. These findings indicate that acute exposure to a 50 Hz magnetic field at 8 mT for short time can impair consolidation of spatial memory.     

Delay-dependent working memory impairment in young-adult and aged 5-HT1BKO mice as assessed in a radial-arm water maze

Serotonin (5-HT) plays a modulatory role in mnemonic functions, especially by interacting with the cholinergic system. The 5-HT1B receptor is a key target of this interaction. The 5-HT1B receptor knockout mice were found previously to exhibit a facilitation in hippocampal-dependent spatial reference memory learning. In the present study, we submitted mice to a delayed spatial working memory task, allowing the introduction of various delays between an exposure trial and a test trial. The 5-HT1BKO and wild-type mice learned the task in a radial-arm water maze (returning to the most recent presented arm containing the escape platform), and exhibited a high level of performance at delays of 0 and 5 min. However, at the delay of 60 min, only 5-HT1BKO mice exhibited an impairment. At a delay of 90 min, all mice were impaired. Treatment by scopolamine (0.8 mg/kg) induced the same pattern of performance in wild type as did the mutation for short (5 min, no impairment) and long (60 min, impairment) delays. The 22-month-old wild-type and knockout mice exhibited an impairment at short delays (5 and 15 min). The effect of the mutation affected both young-adult and aged mice at delays of 15, 30, and 60 min. Neurobiological data show that stimulation of the 5-HT1B receptor inhibits the release of acetylcholine in the hippocampus, but stimulates this in the frontal cortex. This dual function might, at least in part, explain the opposite effect of the mutation on reference memory (facilitation) and delay-dependent working memory (impairment). These results support the idea that cholinergic-serotonergic interactions play an important role in memory processes.     

Anterior but not intralaminar thalamic nuclei support allocentric spatial memory

Medial thalamic damage is a common cause of severe memory disruption in humans. Both the anterior thalamic nuclei (ATN) and the intralaminar thalamic nuclei (ILN) have been suggested as primary sites of diencephalic injury underlying learning and memory deficits, but their respective roles have yet to be resolved. The present study explicitly compared two spatial memory tasks in male PVGc hooded rats with selective neurotoxic lesions to either (1) the ATN or (2) the rostral ILN (and adjacent lateral mediodorsal thalamic nuclei; ILN/LT lesions). As predicted, the ATN group, but not the ILN/LT group, exhibited clear deficits in the Morris water maze task for the initial acquisition of a fixed hidden platform and its reversal to a new position. The second task examined acquisition of egocentric spatial reference memory for a left or right body turn, using any three arms in an 8-arm water maze on any given trial; contrary to predictions, both lesion groups performed as well as the Sham group. The lack of deficits in ILN/LT rats on this second task contrasted with previous findings reporting a detrimental effect of ILN/LT lesions on egocentric working memory. The clear dissociation between the influence of ATN and ILN/LT lesions with respect to allocentric spatial reference memory in the Morris maze emphasizes that caution is required when interpreting the effects of non-ATN thalamic lesions on spatial memory when the lesions encroach substantial areas of the adjacent ATN region.