Ectopic expression of Fgf-4 in chimeric mouse embryos induces the expression of early markers of limb development in the lateral ridge

To determine if estrogen would protect treated rats from deficits in performance on a working memory task across time, 18 female 6-month-old Sprague-Dawley rats were trained to a criterion on a water-escape spatial delayed matching-to-sample problem. Following training, rats were ovariectomized, and nine were maintained on estrogen (polyestradiol-phosphate, 0.5 mg every 3 weeks) and nine on its vehicle for 200 days. After recovery from surgery, the rats were tested for performance every 6 weeks under three conditions: 5 min retention interval (RI); 30 min RI; and 30 min RI with an emotional experience during the RI. Analysis of correct choices revealed that estrogen-treated rats made more correct choices (p < .05) than controls on the 5 min undisturbed interval; estrogen tended to impair performance on the emotionally distracting interval. Estrogen apparently protected working memory on the undisturbed trials and might be pertinent to the maintenance of memory in female mammals.     

Estrogen-induced changes in place and response learning in young adult female rats.

Many findings suggest that changes in circulating estrogen levels influence cognition, in some cases impairing performance and in others enhancing performance. One interpretation of these mixed effects is that estrogen biases the strategy used to solve a task. To test this idea, young adult female rats, ovariectomized for 21 days, were trained after acute hormone or control treatment in 2 very similar tasks with different cognitive requirements. One task required place learning and the other response learning. Rats given two 10-μg injections of estradiol 48 and 24 hr before training learned the place task significantly faster than did rats without estradiol. Conversely, rats without estradiol performed better on the response task than did rats with replacement. These data suggest that the cognitive actions of estrogen may be task-specific by modulating the relative contribution of different learning and memory systems. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Ovarian Hormones and Cognition in the Aged Female Rat: II. Progesterone Supplementation Reverses the Cognitive Enhancing Effects of Ovariectomy.

The authors hypothesized that the progesterone component of some hormone replacement therapies in women is detrimental to cognition. A previous study showed that ovariectomy (ovx) in aged rats enhanced spatial working memory and decreased elevated progesterone levels (H. A. Bimonte-Nelson, R. S. Singleton, C. L. Hunter, et al., 2003). The current study evaluated whether progesterone administration counteracts these cognitive enhancing effects of ovx. Aged sham and aged ovx rats given progesterone exhibited compromised learning of the working and reference memory components of the task, and made more working memory errors on the latter testing days compared with aged ovx rats not given progesterone. Results suggest that whereas ovx of the aged female rat enhances learning and the ability to handle numerous items of spatial working memory information, progesterone is detrimental to these aspects of performance. These findings may speak to studies in menopausal women which suggest that combination hormone therapies have a negative impact on cognition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cholinergic blockade effects on spatial integration versus cue discrimination performance.

Conducted a within-Ss investigation to determine the effects of central vs peripheral cholinergic blockade in 20 male Long-Evans hooded rats tested either on a spatial integration task in which the possibility of rule learning was also available or on a visual discrimination task in which the daily location of food was marked by a distinctive visual stimulus pattern. All testing was conducted on the Maier 3-table apparatus. The only effect of peripheral cholinergic blockade, produced by intraperitoneal atropine methylnitrate (50 mg/kg), was a decrease in exploratory behavior. In contrast, central cholinergic blockade by means of atropine sulfate (50 mg/kg) markedly impaired spatial integration performance. However, it did not impair Ss' ability in rule learning or visual discrimination learning. Central cholinergic blockade impaired Ss' tendency to enter all tables before reentering a given table during the exploratory phase of the daily session. This finding suggests an impairment of working memory for spatial information rather than a general impairment in working memory; this interpretation is applied to the explanation of the deficit in the spatial integration performance. (21 ref) (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)     

Posttraining intrahippocampal estradiol injections enhance spatial memory in male rats: interaction with cholinergic systems

Male Long-Evans rats received an 8-trial training session in a spatial water maze task, followed by a unilateral posttraining intrahippocampal injection of either estradiol (1.0 microgram/0.5 microliter) or saline. Retention was tested 24 hr later, and latency to escape was used as a measure of memory. Retention test escape latencies of rats given intrahippocampal injections of estradiol were lower than those of saline-treated rats, indicating an enhancement of memory. Intrahippocampal injections of estradiol delayed 2 hr posttraining did not affect retention. In Experiment 2, the memory enhancing effect of intrahippocampal injection of estradiol was blocked by peripheral administration of a subeffective dose (0.1 mg/kg) of the cholinergic antagonist scopolamine. Intrahippocampal injections of estradiol enhance memory in male rats, and estradiol may influence memory through an interaction with muscarinic cholinergic systems.     

Differential effect of antipsychotics on place navigation of rats in the Morris water maze. A comparative study between novel and reference antipsychotics

A group of novel neuroleptics (e.g. olanzapine, seroquel, sertindole and ziprasidone) and already marketed compounds (e.g. clozapine, haloperidol and risperidone) were tested for acute effect on spatial learning and memory in Morris' water maze task. Young rats were trained for 4 consecutive days (three trials/day) to find a platform situated beneath the water surface. Two compounds, sertindole and seroquel, were without effect on spatial performance, whereas clozapine impaired performance on the first 2 test days but showed no effect compared to the controls on the last 2 test days. Ziprasidone and olanzapine markedly impaired spatial memory without affecting motor function (measured by the swimming speed). Risperidone and haloperidol also impaired performance but in addition both compounds significantly lowered the swimming speed. The present study indicates that several of the compounds impair spatial learning in Morris water maze. This might be of clinical importance in the treatment of schizophrenics, as many of these patients already show severe cognitive deficits. Therefore, certain antipsychotics could worsen the preexisting memory deficits in schizophrenic patients and this aspect should be considered before antipsychotic treatment.     

Hippocampal seizures disrupt working memory performance but not reference memory acquisition.

The effect of hippocampal seizures in rats was assessed in two spatial memory tasks: The reference memory task was a simultaneous two-choice discrimination in a T-maze. The working memory task was a delayed conditional discrimination in a radial arm maze. In each task the hippocampus of each rat was stimulated to seizure after the presentation of the information to be remembered. In the reference memory task, hippocampal seizures did not impair acquisition, whether the stimulation was given immediately after or 4 hr after the presentation of the stimuli to be remembered. In the working memory task, hippocampal seizures did impair performance in a group of the same rats. These results support the distinction between a trial-dependent working memory system that requires hippocampal function and a trial-independent memory system that does not depend on hippocampal function. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Attention control, memory updating, and emotion regulation temporarily reduce the capacity for executive control.

This research tested the hypothesis that initial efforts at executive control temporarily undermine subsequent efforts at executive control. Four experiments revealed that controlling the focus of visual attention (Experiment 1), inhibiting predominant writing tendencies (Experiment 2), taking a working memory test (Experiment 3), or exaggerating emotional expressions (Experiment 4) undermined performance on subsequent tests of working memory span, reverse digit span, and response inhibition, respectively. The results supported a limited resource model of executive control and cast doubt on competing accounts based on mood, motivation, or task difficulty. Prior efforts at executive control are a significant contextual determinant of the operation of executive processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal and amygdaloid involvement in nonspatial and spatial working memory in rats: Effects of delay and interference.

Parametric manipulations of the task demand were used to examine the role of the hippocampus and amygdala in nonspatial and spatial working memory in male rats. Hippocampal lesions produced an immediate and long-lasting impairment of nonspatial working memory in an operant task. The memory deficits increased as the delay interval and the amount of proactive interference increased. Hippocampal lesions severely impaired spatial working memory in spatial alternation. Extensive postoperative testing reduced the magnitude of impairment of nonspatial but not spatial working memory. Amygdaloid lesions did not impair any aspect of performance in 2 tasks. The results suggest that the hippocampus, but not the amygdala, is involved in working memory and the task demand is a critical determinant for observing impairments of nonspatial working memory following hippocampal lesions. (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)     

Frontal lobe dysfunctions in Korsakoff's syndrome and chronic alcoholism: Continuity or discontinuity?

The effect of long-term heavy alcohol consumption on brain functions is still under debate. The authors investigated a sample of 17 Korsakoff amnesics, 23 alcoholics without Korsakoff's syndrome, and 21 controls with peripheral nerve diseases, matched for intelligence and education. Executive functions were examined for word fluency, the modified Wisconsin Card Sorting Test, an alternate response task, and an "n-back" working memory task. Korsakoff amnesics, but not alcoholics, showed a marked memory impairment. They also scored lower in each of the executive tasks--the alcoholics only in the alternate response task. This task also correlated with the years of the alcohol dependency. First, the authors conclude that Korsakoff's syndrome is associated not only with a memory impairment but also with a global executive deficit. Second, the decline in the ability to alternate between different responses argues for a restricted neurotoxic effect of alcohol on some frontal lobe areas (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditional discriminations based on external and internal cues in rats with cytotoxic hippocampal lesions.

Septal-hippocampal system lesions, mostly using aspiration techniques, have been reported to impair performance of conditional tasks. Rats with axon-sparing cytotoxic, hippocampal lesions were therefore tested in a range of instrumental conditional paradigms. They did not differ from controls in their ability to choose the appropriate object in a conditional object discrimination cued by internal state (hunger or thirst) or on performance of conditional visuospatial object discriminations. Acquisition of a conditional visuospatial discrimination with black and white boxes as stimuli was also unimpaired. In contrast, lesioned rats were profoundly impaired on an open T-maze task when cued by either their internal state (reference memory task) or their previous response (working memory task). The results indicate that perception or use of spatial cues, rather than conditional responding per se, is impaired by cytotoxic hippocampal lesions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Acute administration of interleukin-1β disrupts motor learning.

Proinflammatory cytokines have been shown to disrupt the normal transfer of short-term memory to long-term storage sites. Previous research has focused predominantly on the effect of cytokines on hippocampus-mediated spatial learning. To further understand the effects of cytokines on learning and memory, the authors evaluated the effects of interleukin-1β (IL-1β) on a motor learning task. Male Long-Evans rats were rewarded with food pellets after they traversed a runway. The runway was either flat (control condition) or had up-ended dowels (motor learning condition). Subjects traversed the flat runway or dowel task for 5 days, 10 trials per day, and were treated with either saline or with 4 μg/kg IL-1β immediately after training on the first 2 days. Rats in the motor learning task treated with IL-1β were consistently slower at traversing the runway. IL-1β did not impair performance in the control condition; rats in the flat condition performed similarly regardless of whether they were treated with saline or IL-1β. These data are the first evidence demonstrating IL-1β can disrupt performance in a motor learning task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-term study of chronic oral aluminum exposure and spatial working memory in rats.

The authors report an effort to advance animal models that mimic the cognitive decline of Alzheimer's disease. Rats were trained and repeatedly tested in a spatial delayed matching-to-position paradigm in the water maze, with the location of the submerged platform changing between, but not within, days. After Trial 1 (random search) and intertrial intervals of 30 s or 1 hr, memory was tested in Trial 2. Young rats quickly acquired this task and were repeatedly tested after different intervals over 7 months, with a slight increase in performance toward the end of testing, but no difference in latencies between delays. Oral long-term treatment of 1 group with 0.1 % aluminum caused no delay-dependent working memory deficit. This testing protocol may enable between- and within-subject long-term assessment of spatial working memory before and after drug treatment and may prove useful in animal models of progressive cognitive decline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Microinfusions of neurotensin antagonist SR 48692 within the nucleus accumbens core impair spatial learning in rats.

The involvement of neurotensin (NT) within the nucleus accumbens core (NAC) in behavior has been sparsely investigated. Moreover, little is known of what role NT within the ventral striatum has on spatial learning. The present study investigated whether NT receptors in the NAC are implicated in learning of spatial information. Male Long-Evans rats were trained on a food search spatial learning task. Rats were microinfused with either NT antagonist SR 48692 (50 nM/0.5 =L) or saline in the NAC before each training session. Rats treated with SR 48692 made more reference and working memory errors during the acquisition of spatial learning than did rats infused with saline. These results suggest that NT receptors contribute to NAC-mediated spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial memory deficits in a virtual radial arm maze in amnesic participants with hippocampal damage.

Extensive research with laboratory animals indicates that the hippocampus is crucial for the formation and use of spatial memory. Hippocampal lesions in rodents impair spatial memory on radial arm maze tasks. It is unknown whether amnesic patients with hippocampal damage would exhibit similar impairments on a virtual version of a radial arm maze. To evaluate the importance of the hippocampus in spatial learning and memory, we tested amnesic participants with hippocampal damage in a virtual radial arm maze environment. The virtual radial arm maze required participants to learn and remember 4 rewarded arms of 8 total arms. Spatial learning and memory were assessed using the participants' ability to use salient distal cues in the virtual room to remember the 4 rewarded arms. Amnesic participants' latencies were longer and distance traveled was greater to the rewarded arms compared with nonamnesic participants. Amnesic participants made more errors than nonamnesic participants by either entering nonrewarded arms or by revisiting previously entered arms. These data are analogous to previous animal research. Overall, the human hippocampus is necessary for spatial memory and navigation in a virtual radial arm maze task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Posttraining estrogen and memory modulation

The present paper provides a review of recent research carried out in this laboratory investigating the effects of posttraining peripheral and intrahippocampal injection of estradiol on memory in rats, and estradiol-acetylcholine interactions in memory modulation. Ovariectomized rats received an eight-trial training session in a hippocampal-dependent hidden platform water maze task. Immediately following training, rats received a posttraining peripheral or intrahippocampal injection of estradiol-cyclodextrin complex or vehicle. Twenty-four hours later rats were returned to the maze for a retention test session, and latency to escape was used as a measure of memory for the previous day's training. Peripheral posttraining injection of estradiol enhances memory relative to vehicle-treated rats. Injections of estradiol given 2 h posttraining has no effect on retention, indicating a time-dependent effect of estradiol on memory storage processes. A time-dependent memory enhancing effect of posttraining intrahippocampal injections of estradiol has also been observed in both male and ovariectomized female rats. The memory enhancing effect of peripheral posttraining injection of estradiol in ovariectomized rats is blocked by a subeffective dose of the acetylcholine muscarinic receptor antagonist scopolamine, suggesting that estradiol interacts with cholinergic systems in memory modulation. Concurrent peripheral posttraining injection of a subeffective dose of estradiol and a subeffective dose of the cholinergic agonist oxotremorine produces a synergistic memory enhancing effect. The findings suggest that: (1) estradiol selectively influences memory storage independent of an effect on nonmnemonic processes, (2) the hippocampus is a potential neuroanatomical site of action mediating estrogenic effects on memory, and (3) estradiol interacts with cholinergic systems in memory modulation.     

17-β estradiol administration attenuates deficits in sustained and divided attention in young ovariectomized rats and aged acyclic female rats.

Recent evidence suggests that estrogen may interact with the basal forebrain cholinergic system to influence learning. The authors examined whether the loss of estrogen following ovariectomy (Experiment 1) or the disruption to the estrogen cycle during aging (Experiment 2) impaired performance of the 5-choice serial reaction time task (5-CSRT)--a sustained and divided attention task sensitive to cholinergic challenges in rats. In Experiment 1, posttraining ovariectomy in young rats did not disrupt baseline performance but did impair performance when attention was challenged by variation in the intertrial interval (ITI) or in the intermittent presentation of a novel distracting auditory stimulus. Administration of 17-β estradiol rescued these impairments. Through the use of a within-subjects design, Experiment 2 revealed that 17-β estradiol did not influence the baseline performance of 21-month-old female rats trained on the 5-CSRT task from a young age but did improve performance when attention was challenged by varying the ITI or by presenting a distracting auditory cue. The results indicate that 17-β estradiol administration can improve specific components of attention in young ovariectomized rats and gonadally intact aged female rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial septal lesions in rats produce permanent deficits for strategy selection in a spatial memory task.

Rats with medial septal (MS) lesions have been shown to consistently use a stereotypic response strategy rather than a nonstereotypic spatial learning strategy when solving a radial maze task. The present study examined the long-term effects of MS lesions on spatial memory performance to determine whether MS lesions permanently impair rats from using a nonstereotypic strategy. Male rats, initially trained on a radial maze, were given either MS or sham surgeries and were subsequently retested on the maze. Consistent with previous studies, all Ss with MS lesions used a stereotypic strategy during the postoperative retest. However, when placed through a series of retraining phases that required the S to use a nonstereotypic strategy to solve the task, none of the MS Ss could solve the task. These results indicate that lesions of the MS produce permanent spatial memory deficits that cannot be restored through extensive behavioral training. (PsycINFO Database Record (c) 2010 APA, all rights reserved)