Allocentric spatial and tactile memory impairments in rats with dorsal caudate lesions are affected by preoperative behavioral training.

Rats with caudate lesions and pretrained for 36 trials demonstrated impaired performance on the "reference memory" or invariant aspect of a 12-arm maze and normal performance on the "working memory" or variable aspect of the maze. Rats with caudate lesions and no pretraining were also impaired on an invariant tactile discrimination in a T maze, but they were not impaired on the variable goal-arm choice of the T maze. More extensive preoperative training ameliorated behavioral deficits of rats with caudate lesions in the T maze and radial arm maze. Results showed that behavioral impairment after damage to the caudate is not restricted to egocentric tasks as previously suggested, but the caudate seems to be involved in the initial acquisition that is invariant over many trials. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester on spatial and cued leaning

An investigation was made of the effects of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) on the acquisition and retention of two operantly conditioned discrimination tasks. Twenty Long-Evans rats were conditioned to approach one of two spatial locations that was either held constant across trials (spatial task) or was associated with a visual cue (illuminated lamp) that was randomly assigned to one of the locations on each trial (cued task). Rats were assigned to one of two treatment groups in which they received intraperitoneal injections of either NG-nitro-L-arginine methyl ester or saline approximately 2 h before sessions on each day of training. Analysis was made of the trial-by-trial performance in order to identify the characteristics of learning under each condition. Assessment of learning acquisition was based on the number of trials required to reach a criterion of 80% correct responses, whereas retention was assessed by the number of trials to criterion on each day after the criterion was initially reached. Analysis indicated that treatment groups did not differ significantly on acquisition or retention of either the spatial or cued task. These results indicate that inhibition of nitric oxide synthase does not interfere with the learning or retention of basic operant tasks that involve simple spatial or visual analysis. Whereas results from biochemical and physiological investigations have suggested an impact of nitric oxide synthase on behavioural function, behavioural investigations indicate a limited impact of nitric oxide synthase inhibition on learning and memory. Although these results do not discount the role of nitric oxide synthase in a hippocampal mechanism, they illustrate that behavioural analysis should be made in the context of multiple interacting neural systems. Viewed with previous behavioural research on the effects of NG-nitro-L-arginine methyl ester, these results indicate that nitric oxide synthase inhibition results in impairment of certain forms of learning whereas other forms are preserved.     

Effects of repeated disorientation on the acquisition of spatial tasks in rats: Dissociation between the appetitive radial arm maze and aversive water maze.

This study examined the effects of disorientation on the acquisition of different spatial reference memory tasks. In an appetitively motivated radial arm maze task in which 1 arm was consistently baited, rats that were disoriented before each trial were impaired in their ability to acquire the task relative to rats placed in a clear container and not disoriented. However, disoriented rats were able to learn a Morris water maze and a water version of the radial arm maze under similar training conditions, suggesting that the effects of disorientation may interact with the quality or quantity of motivation involved in a given task. These results suggest that appetitive and aversive spatial tasks are dissociable, and that any impairment that is due to disorientation is specific to the appetitive radial arm maze task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

GluR-A-deficient mice display normal acquisition of a hippocampus-dependent spatial reference memory task but are impaired during spatial reversal.

Acquisition and reversal of a spatial discrimination were assessed in an appetitive, elevated plus-maze task in 4 groups of mice: knockout mice lacking the AMPA receptor subunit GluR-A (GluR1), wild-type controls, mice with cytotoxic hippocampal lesions, and controls that had undergone sham surgery. In agreement with previous studies using tasks such as the water maze, GluR-A-/- mice were unimpaired during acquisition of the spatial discrimination task, whereas performance in the hippocampal group remained at chance levels. In contrast to their performance during acquisition, the GluR-A-/- mice displayed a mild deficit during reversal of the spatial discrimination and were profoundly impaired during discrete trial, rewarded-alternation testing on the elevated T maze. The latter result suggests a short-term. flexible spatial working memory impairment in GluR-A-/- mice, which might also underlie their mild deficit during spatial reversal. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Lesions of basolateral and central amygdala differentiate conditioned cue preference learning with and without unreinforced preexposure.

In the separated arms conditioned cue preference (CCP) task rats are trained by confining them in one arm of an eight-arm radial maze with food and in another arm on the opposite side of the maze with no food on alternate days. After two such trials, rats prefer the food-paired arm when allowed to move freely between the two arms, neither of which contains food. However, if the rats are preexposed to the maze by exploring it without food before training, no preference is observed and at least 4 training trials are required to produce a CCP, suggesting that unreinforced preexposure to the maze latently inhibits acquisition. If this interpretation is correct, preexposure should reduce the size of the preference acquired with both 2 and 4 training trials. In Experiment 1, this prediction was replicated for 2 training trials; however, with 4 training trials, eliminating preexposure also eliminated the CCP. A previous finding that basolateral amygdala lesions impair the CCP with preexposure and 4 training trials was replicated in Experiment 2, but similar lesions had no effect on the CCP in nonpreexposed rats given 2 training trials. In contrast, lesions of the central nucleus impaired the 2 training trial CCP but had no effect on the 4 training trial CCP. This double dissociation suggests that the BLA-mediated 4 training trial CCP may be due to learning about the reward features of the maze space, while the central-nucleus-mediated 2 training trial CCP may be due to a conditioned approach response. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Further studies of hippocampal representation during odor discrimination learning.

The contribution of hippocampal and nonhippocampal memory processing to simultaneous-cue odor discrimination learning was assessed. In this task rats with hippocampal system damage consequent to fornix lesions (fornix rats) were severely and persistently impaired in discrimination learning, acquisition of learning set, and concurrent discrimination, although they occasionally solved some problems at a normal rate. By using those problems on which fornix rats succeeded, to permit comparisons of performance strategies with normal rats, differences between groups were shown on response latency measures and on probe trials involving the novel pairing of familiar odors. Normal rats had a bimodal distribution of response latencies, and their latency depended on where the S+ was presented. Fornix rats had short response latencies and responded equally quickly wherever the S+ was presented. Furthermore, when the representation of familiar S+ and S– odor pairs was challenged in probe trials, normal rats responded appropriately to the correct stimulus, whereas fornix rats behaved as if presented with a new odor pair. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A triple dissociation of memory systems: Hippocampus, amygdala, and dorsal striatum.

Investigated the respective roles of the hippocampus (H), the amygdala (A), and the dorsal striatum (DS) in learning and memory. A standard set of experimental conditions for studying the effects of lesions to the 3 brain areas using an 8-arm radial maze was used: a win-shift (W-SH) version, a conditioned cue preference (CCP) version, and a win-stay (W-ST) version. Damage to the hippocampal system impaired acquisition of the W-SH task but not the CCP or W-ST tasks. Damage to the lateral A impaired acquisition of the CCP task but not the W-SH or W-ST tasks. Damage to the DS impaired acquisition of the W-ST task but not the W-SH or CCP tasks. Results are consistent with the hypothesis that the mammalian brain may be capable of acquiring different kinds of information with different, more-or-less independent neural systems (NSs). A NS that includes the H may acquire information about the relationships among stimuli and events. An NS that includes the A may mediate the rapid acquisition of behaviors based on biologically significant events with affective properties. An NS that includes the DS may mediate the formation of reinforced stimulus–response associations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the dorsomedial striatum in behavioral flexibility for response and visual cue discrimination learning.

These experiments examined the effects of dorsomedial striatal inactivation on the acquisition of a response and visual cue discrimination task, as well as a shift from a response to a visual cue discrimination, and vice versa. In Experiment 1, rats were tested on the response discrimination task followed by the visual cue discrimination task. In Experiment 2, the testing order was reversed. Infusions of 2% tetracaine did not impair acquisition of the response or visual cue discrimination but impaired performance when shifting from a response to a visual cue discrimination, and vice versa. Analysis of the errors revealed that the deficit was not due to perseveration of the previously learned strategy, but to an inability to maintain the new strategy. These results contrast with findings indicating that prelimbic inactivation impairs behavioral flexibility due to perseveration of a previously learned strategy. Thus, specific circuits in the prefrontal cortex and striatum may interact to enable behavioral flexibility, but each region may contribute to distinct processes that facilitate strategy switching. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Learning and Retrieval of Concurrently Presented Spatial Discrimination Tasks: Role of the Fornix.

In macaque monkeys (Macaco mulatta), memory for scenes presented on touch screens is fornix dependent. However, scene learning is not a purely spatial task, and existing direct evidence for a fornix role in spatial memory comes exclusively from tasks involving learning about food-reward locations. Here the authors demonstrate that fornix transection impairs learning about spatial stimuli presented on touch screens. Using a new concurrent spatial discrimination learning task, they found that fornix transection did not impair recall of preoperatively learned problems. Relearning, on the other hand, was mildly impaired, and new learning was strongly impaired. New learning of smaller sets of harder problems was also markedly impaired, as was spatial configured learning. This pattern supports a functional specialization according to stimulus domain in the medial temporal lobe. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning and performance in the radial arm maze is impaired after N-methyl-{d}-aspartate (NMDA) receptor blockade in striatal subregions.

These experiments addressed the role of striatal N-methyl-{d}-aspartate (NMDA) receptors in spatial behavior in the radial arm maze. Rats treated with the NMDA antagonist D-2-amino-5-phosphonopentanoic acid (AP-5) in the nucleus accumbens core, medial caudate, and posterior caudate were all significantly impaired in acquiring the correct spatial responses. In contrast, rats infused with AP-5 in the nucleus accumbens shell showed little impairment. When rats in all groups had learned the maze and were performing at similar levels, AP-5 had relatively little effect except in the posterior caudate group, where errors and trial times were again increased. These findings demonstrate the importance of NMDA receptor-dependent activity within the accumbens and caudate in spatial learning and performance. The neural processes necessary for adaptive spatial learning in complex environments may recruit multiple cortical systems having specialized functions, which in turn are integrated in widespread striatal regions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modulation of the Impairment of Hippocampectomized Rats on the Radial-Arm Maze Cue Task by Visual Characteristics and Subicular Damage.

Rats with N-methyl-D-aspartate lesions of the hippocampus that partially damaged the subiculum and controls were trained on 2 versions of the radial-arm maze cue task, with either proximal or distal visual stimuli. In Experiment 1, the relative positions of the stimuli varied across trials. Lesioned rats were impaired when trained on the distal version, as opposed to transiently slowed down when trained on the proximal version. In Experiment 2, the relative positions of the stimuli were fixed throughout training. Lesioned rats were impaired when trained on the distal or the proximal version. Further analyses showed that combined damage to the hippocampus and the subiculum was required to impair performance in the proximal, but not the distal, version. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effects of NMDA lesions centered on the postrhinal cortex on spatial memory tasks in the rat.

Rats with bilateral N-methyl-D-aspartate lesions centered on the postrhinal cortex (POR) and sham lesions were tested in a series of spatial memory tasks. The POR-lesioned rats were significantly impaired compared with sham rats in the reference memory version of both the water maze and radial arm maze tasks and in the standard radial arm maze working memory task. The POR-lesioned rats displayed a delay-independent impairment in the working memory versions of the water maze and in a delayed nonmatching-to-place (DNMP) version of the radial arm maze task. The POR-lesioned rats were also impaired in a DNMP procedure conducted in the T-maze. These findings indicate that the POR has a delay-independent role in the processing of spatial information. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Role of the dorsal prestriate cortex in visuospatial configural discrimination by monkeys

Cynomolgus monkeys (Macaca fascicularis) learned a series of visuospatial configural discriminations in which particular discriminative stimulus objects were rewarded only in particular spatial locations. For example, object X was rewarded if it was on the left but not if it was on the right. After ablation of part of the dorsal prestriate cortex they were impaired in learning discriminations of this kind. The same animals were not impaired in learning visual object discriminations in which spatial position was irrelevant, nor in learning spatial discriminations in which object identity was irrelevant. The results were compared with previously reported results from fornix transection in the same tasks; the deficit following dorsal prestriate ablation in visuospatial configural discrimination learning was similar in severity to that which followed fornix transection. The results show that the dorsal prestriate area has a more general role in visuospatial processing than was known hitherto, and they suggest that it interacts with the hippocampal formation and fornix in visuospatial memory tasks.     

Mediodorsal thalamic lesions impair radial maze performance in the rat.

The role of the mediodorsal thalamic nucleus (MD) in spatial memory processes was assessed. Animals were preoperatively trained on an 8-arm maze placed in a visually deprived environment. Following 50 acquisition trials, one group received bilateral electrolytic lesion of the MD thalamus, whereas the other group received sham lesions. On postoperative tests of radial maze performance, MD lesioned animals made significantly more errors, made more errors sooner, and emitted fewer correct responses before making an error than did sham controls. The lesioned subjects also exhibited considerable perseveration immediately postoperation and developed response patterning on postlesion trials. Lesions of the mediodorsal thalamus may fundamentally compromise memory systems and alter ability to respond appropriately in a minimally cued environment. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Fornix lesions can facilitate acquisition of the transverse patterning task: a challenge for "configural" theories of hippocampal function

Configural theories of hippocampal function predict that hippocampal dysfunction should impair acquisition of the transverse patterning task, which involves the concurrent solution of three discrimination problems: A+ versus B-; B+ versus C-; and C+ versus A-. The present study tested this prediction in rats using computer-graphic stimuli presented on a touchscreen. Experiment 1 assessed the effects of fornix lesions when the three problems were introduced sequentially (phase 1: A+ vs B-; phase 2: A+ vs B-, B+ vs C-; phase 3: A+ vs B-, B+ vs C-, C+ vs A-). Fornix lesions significantly facilitated acquisition of the complete transverse patterning task (phase 3) but had no effect on the number of sessions or errors required to attain criterion during phase 1 or phase 2. In experiment 2, in which all three problems were presented concurrently from the outset of training, fornix-lesioned animals outperformed control animals during the seventh block of acquisition trials and were not impaired during any stage of acquisition. Importantly, these same animals were significantly impaired on two allocentric spatial tasks: T-maze alternation (experiments 1 and 2) and the Morris Swim Task (experiment 1). These results contradict the predictions of configural theories of hippocampal function and cast doubt on the popular notion that spatial learning is a special case of configural learning.     

The biology of menopause

Rats with bilateral electrolytic lesions of perirhinal cortex (PRC) or sham control (SHAM) lesions were tested in spatial reference and working memory tasks in the radial arm maze. In experiment 1, one arm of the maze was baited and always located in a fixed position relative to the extra-maze environment. PRC lesioned animals made a significantly greater number of errors than did SHAM animals during initial training in this reference memory task and exhibited a delay-dependent impairment on trial 5 in a series when a delay period of 5, 60, 120, or 240 s was inserted between trials 4 and 5. In experiment 2, when a second group of the animals was tested on the standard radial arm maze working memory task, the performance of the PRC group was markedly impaired relative to controls. These data demonstrate that electrolytic PRC lesions result in a deficit in both spatial reference and spatial working memory tasks. These effects are interpreted as being consistent with the idea that PRC plays an important role in episodic memory processes. These processes may include the storage of information, which is required for the performance of spatial tasks.     

On the Transience of Egocentric Working Memory: Evidence From Testing the Contribution of Limbic Brain Regions.

Rats trained on a nonmatching-to-turn rule revealed that egocentric working memory is readily disrupted, hard to use, and transient. In Experiment 1, rats failed to acquire the rule in a plus-maze. Experiment 2 used 2 different plus-mazes to remove any intramaze cues. Task acquisition occurred only when rats could use direction cues (i.e., nonegocentric cues). In Experiments 3 and 4, a J maze was used to minimize the retention interval and eliminate handling rats within a trial. All rats acquired the nonmatching rule, although a 3-s retention delay severely impaired performance. Fornix lesions transiently disrupted performance of the J-maze task (Experiments 3 and 4), but neither fornix (Experiment 1) nor retrosplenial (Experiment 2) lesions impaired the plus-maze tasks. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex-related differences in cortical function after medial frontal lesions in rats.

The effects of sex on the performance of 4 spatial mazes (Morris water task, landmark task, radial arm maze, and egocentric radial arm maze) were studied in male and female rats given medial frontal lesions. Operated rats from both sexes were impaired at all of the tasks, but the frontal males were much less impaired than frontal females on the Morris task and the radial arm maze, both of which require animals to use multiple visual-spatial cues for their successful solution. Males also performed better on the egocentric maze. In contrast, frontal females performed better than frontal males at the landmark task, which is best solved by using a single spatial cue. The only sex difference in unoperated rats was a small advantage for females on the egocentric task. The sex differences may reflect an underlying difference in cortical organization or a differential response to cortical lesion in males and females. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Primate basal ganglia activity in a precued reaching task: preparation for movement

Single cell activity was recorded from the primate putamen, caudate nucleus, and globus pallidus during a precued reaching movement task. Two monkeys were trained to touch one of several target knobs mounted in front of them after an LED was lighted on the correct target. A precue was presented prior to this target "go cue" by a randomly varied delay interval, giving the animals partial or complete advance information about the target for the movement task. The purpose of this design was to examine neuronal activity in the major structures of the basal ganglia during the preparation phase of limb movements when varying amounts of advance information were provided to the animals. The reaction times were shortest with complete precues, intermediate with partial precues, and longest with precues containing no information, demonstrating that the animals used precue information to prepare partly or completely for the reaching movement before the target go cue was given. Changes in activity were seen in the basal ganglia during the preparatory period in 30% of neurons in putamen, 31% in caudate nucleus, and 27% in globus pallidus. Preparatory changes were stronger and more closely linked to the time of movement initiation in putamen than in caudate nucleus. Although the amount of information contained in the precues had no significant effect on preparatory activity preceding the target go cue, a directional selectivity during this period was observed for a subset of neurons with preparatory changes (15% in putamen, 11% in caudate nucleus, 14% in globus pallidus) when the precue contained information about the upcoming direction of movement. A smaller subset of neurons showed selectivity for the preparation of movement amplitude. A larger number of preparatory changes showed selectivity for the direction or amplitude of movement following the target go cue than in the delay period before the cue. The intensity of preparatory changes in activity in many cases depended on the length of the delay interval preceding the target go cue. Even following the target go cue, the intensity of the preparatory changes in activity continued to be significantly influenced by the length of the preceding delay interval for 11% of changes in putamen, 8% in caudate nucleus, and 18% in globus pallidus. This finding suggests that preparatory activity in the basal ganglia takes part in a process termed motor readiness. Behaviorally, this process was seen as a shortening of reaction time regardless of precue information for trials in which the delay interval was long and the animals showed an increased readiness to move.(ABSTRACT TRUNCATED AT 400 WORDS)     

Systematic comparison of the effects of hippocampal and fornix-fimbria lesions on acquisition of three configural discriminations

The effects of lesions to the hippocampal system on acquisition of three different configural tasks by rats were tested. Lesions of either the hippocampus (kainic acid/colchicine) or fornix-fimbria (radiofrequency current) were made before training. After recovery from surgery, rats were trained to discriminate between simple and compound-configural cues that signaled the availability or nonavailability of food when a bar was pressed. When positive cues were present, one food pellet could be earned by pressing a lever after a variable time had elapsed. The trial terminated on food delivery (variable interval 15 s). This procedure eliminates some possible alternative explanations of the results of previous experiments on configural learning. Hippocampal lesions increased rates of responding and retarded acquisition of a negative patterning task (A+, B+, AB-); using a ratio measure of discrimination performance these lesions had a milder retarding effect on a biconditional discrimination (AX+, AY-, BY+, BX-), and they had no effect on a conditional context discrimination (X: A+, B-; Y: A-, B+). Fornix-fimbria lesions did not affect acquisition of any of these tasks but increased rates of responding. The results suggest that several task parameters determine the involvement of the hippocampus in configural learning; however, all tasks tested can also be learned to some extent in the absence of an intact hippocampal system, presumably by other learning/memory systems that remain intact following surgery. The lack of effect of fornix-fimbria lesions on any of these tasks suggests that retrohippocampal connections with other brain areas may mediate hippocampal contributions to the learning of some configural tasks. An analysis of these results and of experiments on spatial learning situations suggests that involvement of the hippocampus is a function of the degree to which correct performance depends on a knowledge of relationships among cues in a situation.