Spatial and nonspatial learning across the rat estrous cycle.

Recent evidence has demonstrated that there are fluctuations in both the anatomy and physiology of the hippocampus across the estrous cycle of the female rat. In the present study we examined the behavioral implications of these changes by testing females on either a hippocampal or nonhippocampal version of the Morris water maze during the various phases of the estrous cycle. Males were also tested on these tasks. Although there was little variance on the nonhippocampal cue task, females in proestrus performed significantly better than those in estrus. Optimal female performance on the spatial version of the task occurred during the phase of estrus, whereas the least efficient performance occurred during proestrus. These results do not support the traditional view that hippocampal long-term potentiation is positively correlated with spatial learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial attention and implicit sequence learning: Evidence for independent learning of spatial and nonspatial sequences.

This research investigated whether regular spatial orienting sequences can be learned implicitly and independently of response requirements. In a new version of a serial response task introduced by M. J. Nissen and P. Bullemer (1987) participants had to discriminate between objects that could occur at different locations. Independent sequences determined the succession of locations and objects. Even participants who were not aware of any regularities exhibited evidence for learning of both sequences (Experiment 1). Experiment 2 showed that the joint learning of spatial and object sequences was as efficient as learning of single sequences and that it even occurred when learning required memory for past sequence elements and attention was blocked through a secondary tone-counting task. Results are consistent with the idea that independent systems may exist for the implicit acquisition of spatial and nonspatial regularities. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immediate and long-term effects of neonatal MK-801 treatment on nonspatial learning

These experiments observed the immediate and long-term effects of neonatal treatment with MK-801 on patterned single alternation (PSA), a form of nonspatial, memory-based learning. Rat pups were injected daily on postnatal days (PND) 7-19, with MK-801 (MK+) or the less active isomer of MK-801 (MK-) (0.25 mg/kg), and trained at either PND 22 or 60. Rats treated with MK+ or MK- and trained on PND 22 were significantly impaired in PSA when compared with the saline control. Beyond the learning impairment, MK+ rats showed an overall decreased running speed during training. They also presented an array of abnormal behaviors and significant weight loss. These nonassociative variables were determined for several doses (0.025, 0. 05, 0.1, 0.15, and 0.20 mg/kg) through PND days 22-25. Rats that received the threshold dose for secondary effects (0.025 mg/kg) also showed an overall decrease in running speed, but failed to show a significant nonspatial learning impairment on PSA. The PSA learning impairment was found to be not long lasting; rats trained at PND 60, after neonatally receiving the original high dose of MK-801, did not differ from controls.     

Spatial versus nonspatial relational learning in free-ranging fox squirrels (Sciurus niger).

This experiment was designed to assess spatial and nonspatial relational learning in free-ranging squirrels. The authors tested the possible use of proximal landmarks as conditional information to predict the locations of nuts, hidden in small dishes distributed on a plastic board. Squirrels were trained to associate the presence of 1 object, at the center of the board, with 1 set of baited dishes, whereas the presence of a 2nd object, placed alternatively at the same location, was associated with another set of dishes. They did not acquire the nonspatial relational task on the basis of proximal landmarks. They developed a win-stay spatial strategy relying on directional information derived from distant visuospatial cues and neglected proximal spatial information when it conflicted. They relied on their memory of the food locations in the previous trial to predict the nuts' locations, even though the objects were the only predictors of these locations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning and hippocampal volume in male deer mice: relations to age, testosterone and adrenal gland weight

Endoscopic carpal tunnel release is a controversial procedure used in the treatment of carpal tunnel syndrome. Although endoscopic carpal tunnel release is associated with less incisional pain and faster recovery time than the open carpal tunnel release, opponents of endoscopic carpal tunnel release suggest that its benefits are outweighed by its higher complication rates from median nerve transection and transient numbness of the fingers. Because of the huge economic and social impact of carpal tunnel syndrome in this country, we performed a cost-effectiveness analysis comparing endoscopic carpal tunnel release and open carpal tunnel release using guidelines established by the Panel on Cost-Effectiveness in Health and Medicine of the U.S. Public Health Service. A decision analytic model was used to measure differences in cost and effectiveness--expressed as quality-adjusted life-years (QALYs)--between endoscopic carpal tunnel release and open carpal tunnel release. The societal perspective was chosen, and probabilities for various outcomes for the two procedures were obtained from published randomized-controlled trials. Cost data were derived from the Medicare Resource-Based Relative Value Units published in the Federal Register. QALYs were obtained from two groups of health care providers using a utility-assessment questionnaire. Using probabilities for various outcomes from the two published randomized-controlled trials comparing endoscopic carpal tunnel release and open carpal tunnel release, we constructed a decision tree to derive both the cost and the QALYs for the two procedures. The incremental cost difference between endoscopic carpal tunnel release and open carpal tunnel release was $46, using Medicare cost and probabilities of various outcomes derived from a study by Brown et al. in 1993. We calculated QALYs for five age groups--25, 35, 45, 55, 65--assuming a life expectancy of 75 years. The marginal effectiveness (QALY of endoscopic carpal tunnel release minus QALY of open carpal tunnel release) ranged from 0.235 QALY for the 25-year-old age group to 0.066 QALY for the 65-year-old age group, giving a cost-effectiveness ratio of $195/QALY and $693/QALY, respectively. When compared with other accepted medical interventions such as breast cancer screening ($4836/QALY) and exercise to prevent coronary heart disease ($13,508/QALY), endoscopic carpal tunnel release seems to be cost-effective. However, our sensitivity analysis indicated that the cost-effectiveness ratio was very sensitive to a major complication such as median nerve injury. For endoscopic carpal tunnel release to be a cost-effective procedure, the incidence of median nerve injury must be one percentage point less for endoscopic carpal tunnel release than for open carpal tunnel release. Based on the data from the randomized-controlled trials, endoscopic carpal tunnel release seems to be a cost-effective procedure; however, before it can be recommended, greater emphasis must be given to the training of surgeons in this new technique, so that major complications such as median nerve injuries can be avoided. In addition, future studies must better define the actual incidence of nerve injuries for both endoscopic carpal tunnel release and open carpal tunnel release in the community setting.     

Spatial reversal learning in preclinical scrapie-inoculated mice

Acquisition and reversal of a two-choice spatial discrimination were tested in scrapie-inoculated mice. Both acquisition and reversal were normal in mice tested 138 and 103 days prior to the onset of clinical symptoms. At 65 days before onset of clinical symptoms, scrapie-inoculated mice required more trails to criterion in reversal learning, but this effect was not significant in a second experiment (68 days preclinical) and was transient: no effect was seen 33 days before symptoms. However, the course of reversal learning was abnormal in all three late preclinical groups (68, 65 and 33 days before symptoms). Reversal learning in these three groups was characterized by a rapid extinction of the original discrimination, followed by a period, absent in controls, during which performance showed no further improvement. This effect corresponds in time of onset to the appearance of characteristic neuropathological features.     

Cerebral emboli and serum S100beta during cardiac operations

BACKGROUND: The glial protein S100beta has been used to estimate cerebral damage in a number of clinical settings. The purpose of this investigation was to determine the correlation between cerebral microemboli and S100beta levels during cardiac operations. METHODS: Transcranial Doppler ultrasonography was used to measure emboli in the right middle cerebral artery. Emboli counts (n = 111) were divided into five time periods: (1) incision to aortic cannulation; (2) aortic cannulation to cross-clamp onset; (3) cross-clamp onset to cross-clamp release; (4) cross-clamp release to decannulation; and (5) decannulation to chest closure. The level of S100beta (n = 156) was measured at baseline, at the end of cardiopulmonary bypass, then 150 and 270 minutes after cross-clamp release. RESULTS: The level of S100beta correlated with age, cardiopulmonary bypass time, cross-clamp time, and number of emboli at time period 2. Although cardiopulmonary bypass time was univariately associated with S100beta level, it became nonsignificant in a multivariable model that included age and cross-clamp time. CONCLUSIONS: The correlation of S100beta level with emboli measured during cannulation (time period 2) supports the hypothesis that cannulation is a high-risk time period for cerebral injury.     

Cloning, overexpression, purification, and spectroscopic characterization of human S100P

OBJECTIVES: We sought to study the renal circulatory effects of adenosine in patients with chronic congestive heart failure (CHF). BACKGROUND: Renal blood flow (RBF) is often reduced in patients with chronic CHF and may lead to decreased renal function. The cause of reduced RBF is multifactorial and involves systemic as well as local vasoregulatory mechanisms. Stimulation of renal adenosine A1 receptors in animal models has resulted in a significant vasoconstriction of afferent and efferent glomerular arterioles and deterioration of renal function. Although adenosine serum levels have been shown to be elevated in patients with CHF, their effect on the renal circulation in this patient population has not been studied. METHODS: Nine patients with CHF from left ventricular systolic dysfunction were studied. The effects of adenosine at a dose of 10(-5) mol/liter infused directly into the main renal artery on heart rate, renal artery blood pressure, renal artery cross-sectional area (measured by intravascular ultrasound), renal Doppler blood flow velocity (measured by a Doppler flow wire in the renal artery), RBF and renal vascular resistance (RVR) were evaluated. RESULTS: Infusion of adenosine resulted in no significant effect on heart rate or renal artery blood pressure but caused a substantial increase in RVR (11,204 +/- 1,469 to 31,494 +/- 3,911 dynes x s x cm(-5), p = 0.0005), which led to a marked fall in RBF in every patient (mean values 376 +/- 36 to 146 +/- 22 ml/m2, p = 0.0002). These changes in RVR and RBF were associated with no significant change in renal artery cross-sectional area (0.389 +/- 0.040 to 0.375 +/- 0.033 cm2, p = 0.3). CONCLUSIONS: Stimulation of renal adenosine receptors in patients with CHF results in marked renal vasoconstriction that leads to an important reduction in RBF. Lack of change in renal artery cross-sectional area suggests that adenosine affects intrarenal resistance blood vessels rather than large conductance vessels. These results may indicate a rationale for investigation of renal adenosine receptor blockade for enhancement of RBF and improvement of renal function in patients with chronic CHF.     

Interactive effects of age and familiarization in paired-associate learning.

Prior to learning a list of paired associates consisting of pictures of common objects, 40 preschool and 40 2nd graders were given 1 of 4 familiarization conditions: stimulus pretraining, response pretraining, irrelevant pretraining, and no pretraining. Results show that the 2nd graders exhibited positive transfer from familiarization to paired-associate learning due to nonspecific factors such as "warm-up." The preschoolers, however, displayed positive transfer due to more specific factors inherent in response and stimulus pretraining. These results suggest that the pretraining experience facilitated rehearsal by making available verbal labels. Results are consistent with (a) developmental hypotheses that emphasize growth in discriminative capacity and/or verbal mediation and (b) phase theories of paired-associate learning that emphasize stimulus and response learning stages. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning and memory as a function of age in the dog.

Spatial learning and memory were studied in dogs of varying ages and sources. Compared to young dogs, a significantly higher proportion of aged dogs could not acquire a spatial delayed nonmatching-to-sample task. A regression analysis revealed a significant age effect during acquisition. Spatial memory was studied by comparing performance at delay intervals of 20, 70, and 110 s. At short delays aged and young dogs were similar; at longer delays, errors increased to a greater extent in old than in young dogs; however, this was not statistically significant. It was possible to identify 2 groups of aged animals, age-impaired and age-unimpaired. Several of the dogs were also tested on an object recognition memory task, which was more difficult to learn than the spatial task. The possibility that these findings are confounded by breed differences is considered. Overall, the present results provide further evidence of the value of a canine model of aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Testosterone potentiates scopolamine-induced disruptions of nonspatial learning in gonadectomized male rats.

Whereas research into the effects of the gonadal hormones on learning and memory has primarily focused on estrogen in females, recent evidence suggests that testosterone can also modulate learning in males through an interaction with the cholinergic system. In the present study, the interactive effects of testosterone and scopolamine (0.1- 0.32 mg/kg), a muscarinic receptor antagonist, on complex behavioral processes were investigated in male rats trained to respond under a multiple schedule of repeated acquisition and performance. In the acquisition component, subjects acquired a different 3-response sequence each session, whereas in the performance component, they responded on the same 3-response sequence each session. Although gonadectomy did not disrupt responding in either component, gonadectomized rats were less sensitive to the disruptive effects of scopolamine on both response rate and accuracy. In contrast, after receiving exogenous testosterone replacement, these gonadectomized males were more sensitive to the behavioral disruptions produced by scopolamine (i.e., the effects of scopolamine were similar to those obtained in gonadally intact males). These results suggest that testosterone replacement can enhance scopolamine-induced behavioral effects in gonadectomized male rats responding under a multiple schedule of repeated acquisition and performance, a finding that is in contrast to those previously found for certain spatial tasks. Furthermore, the present findings suggest that testosterone may decrease the activity of the cholinergic system during nonspatial tasks and thereby work in concert with the antagonism produced by scopolamine. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Estradiol replacement in gonadectomized male rats alters scopolamine-induced disruptions of nonspatial learning.

Recent evidence indicates that testosterone can modulate learning in males through an interaction with the cholinergic system. However, the mechanism for this interaction between testosterone and the cholinergic system on learning remains uncharacterized and may involve several of testosterone's active metabolites. In the present study, two of the active metabolites of testosterone, 5α-dihydrotestosterone and estradiol, were administered in combination with the muscarinic receptor antagonist scopolamine (0.1-1 mg/kg, i.p.) to adult gonadectomized male rats that were trained to respond under a multiple schedule of repeated acquisition and performance of response sequences. In the acquisition component, subjects acquired a different three-response sequence each session, whereas in the performance component they responded on the same three-response sequence each session. When scopolamine was administered, it produced greater rate-decreasing and error-increasing effects in gonadally intact subjects than in gonadectomized subjects, even though gonadectomy had little or no effect on these measures under control conditions. In gonadectomized rats receiving 5α-dihydrotestosterone replacement, the disruptions produced by scopolamine were also smaller than those produced in gonadally intact subjects. In contrast, gonadectomized rats receiving estradiol replacement were as sensitive, or more sensitive, to scopolamine-induced disruptions of response rate and accuracy than those under the gonadally intact condition. These results suggest that testosterone's interactive effects with the cholinergic system on learning in gonadectomized male rats may not be mediated directly via androgen receptors, but rather by estrogen receptors following the aromatization of testosterone to estradiol. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alpha2C-adrenoceptor-overexpressing mice are impaired in executing nonspatial and spatial escape strategies

Blood flow in response to bradykinin (BK, B2 receptor agonist) and desArg9 BK (B1 receptor agonist) was measured by laser Doppler flowmetry, as a reversal of noradrenaline (50 nmol)-induced decreased blood flow, in the synovium of the anaesthetised rabbit. Either a pretreatment (-6 h) of the cytokines IL-1beta (10 pmol) plus TNFalpha (10 pmol) or saline was injected intra-articularly. BK increased blood flow irrespective of pretreatment, whereas desArg9BK increased blood flow only in the cytokine-pretreated joints. The B2 antagonist HOE 140 reversed (p < 0.01) only the BK responses, and the B1 antagonist desArg9Leu8BK only reversed desArg9BK responses (p < 0.001). A nitric oxide synthase inhibitor, (L-NAME, 10 micromol kg(-1)), reversed the effects of the kinins (p < 0.05), but not sodium nitroprusside-stimulated responses. The results suggest that the B2 receptor is constitutively expressed and that the B1 receptor can mediate responses in inflamed tissues. The results, in addition, indicate that the responses, mediated via both receptors, are nitric oxide-dependent.     

Effects of ketamine and L-glutamic acid diethyl ester on spatial and nonspatial learning tasks in rats

1. Current concepts in the regulation of atrial contractility by non-adrenergic non-cholinergic (NANC) sensory nerves are reviewed. 2. There is now evidence that in addition to sympathetic and parasympathetic innervation capsaicin-sensitive sensory nerves contribute to the local control of atrial contractility by releasing NANC transmitters, such as calcitonin gene-related peptide (CGRP). 3. Certain chemical and physical stimuli affect atrial contractility by inducing the release of CGRP from sensory nerves. In addition, as widely recognized for the sympathetic and vagal atrial innervation, NANC neurotransmission is under the inhibitory control of several endogenous modulators. 4. Cardioexcitatory actions of NANC neurotransmission on the atrial myocardium are considered. 5. Pharmacological modulation of NANC neurotransmission and functional evidence for cross-talk between NANC and sympathetic neurones are also discussed.     

Serial position effects and duration of memory for nonspatial stimuli in rats.

Recognition memory for lists of nonspatial items was tested in rats using a nonmatching-to-sample task. The recency effect at short retention intervals disappeared as the interval increased, but primacy did not develop although responding was still above chance up to 2 hr after 10-s sample times. Neither proactive nor retroactive interference was apparent. Rats transferred the nonmatching-to-sample rule to completely novel stimuli. The study failed to replicate the prominent U-shaped serial position curve found in a similar study by P. Reed, T. Chih-Ta, J. P. Aggleton, and J. N. P. Rawlins (1991), for which E. A. Gaffan and D. Gaffan (1992) had found the data less variable than expected. Evidence of primacy in this procedure remains insubstantial. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Spatial learning deficits in mice with a targeted glucocorticoid receptor gene disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

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

In order to evaluate the functional role of chemotactic cytokines in the regulation of brain function, we examined the effects of acidosis on the production of IL-8 in cultured neurons and/or astrocyte-rich cerebellar granule cells as assessed by the ELISA method. A time-dependent and significant production of IL-8 was detected in the extracellular fluid of astrocyte-rich cultured cells at 2, 3 and 6 hrs after treatment with acidified Krebs-HEPES buffer (pH 6.9), although such production did not appear in the fluid of neuron-rich cells. Additionally, microglia were detected by microscopic examination in both cultured cells under acidotic conditions. Only astrocyte-containing cultured cells produced a marked increase in intracellular IL-8 under acidotic conditions, although this production was much less than that seen in the extracellular fluid at 6 hrs under acidosis. The increase of IL-8 in astrocyte-rich cultures induced by acidosis was potentiated by treatment with glutamate, which enhanced the increase of cytosolic Ca2+ levels under acidosis, and was affected by extracellular Ca2+ conditions, by cyclosporine A, an inhibitor of calcineurin, and by trifluoperazine, an inhibitor of phospholipase A2. Significant inhibition of IL-8 production was detected after 6 hrs of pretreatment with trifluoperazine. Furthermore, the production of IL-8 under acidosis was associated with the appearance of astrocyte damage. These results suggest that Ca2+-dependent IL-8 is produced by astrocytes, but not neuronal cells, under acidosis, and that this production may be related to the process of cell dysfunction resulting from membrane destruction induced by acidosis.     

A comparison between the effects of medial septal lesions and entorhinal cortex lesions on performance of nonspatial working memory tasks and reversal learning

Two studies explored the relationship between cognitions and long-term symptoms in adult child sexual abuse (CSA) survivors. In Study 1, an American sample of 43 survivors completed questionnaires assessing attributional style and dysfunctional beliefs in cognitive themes affected by victimization, as well as measures of posttraumatic symptoms. Survivors' attributions of negative events were more internal, stable, and global than those of 29 comparison subjects without a history of CSA. However, only the globality scale was significantly related with severity of long-term symptoms. High correlations between dysfunctional beliefs concerning safety, trust, esteem, or intimacy, and posttrauma symptoms were found. The latter finding was replicated in Study 2 with a German sample of 35 CSA survivors, even when controlling for frequency of abuse.     

Influence on Simon and SNARC effects of a nonspatial stimulus-response mapping: Between-task logical recoding.

In 4 experiments, we intermixed trials in which the stimulus color was relevant with trials where participants had to judge the stimulus shape or parity and found that the logical-recoding rule (Hedge & Marsh, 1975) applied to the relevant dimension in a task can generalize to the irrelevant dimension of the other task. The mapping assigned to participants in color-relevant trials modulated the Simon and SNARC (spatial-numerical association of response codes) effects (Simon & Small, 1969; Dehaene, Bossini, & Giraux, 1993) observed in shape- and parity-relevant trials. Standard effects were obtained when color-relevant trials required participants to respond by pressing a key of the same color as the stimulus, whereas an alternate-color mapping caused either the disappearance or reversal of the effects. The present results demonstrate that for between-task transfer effects to occur the critical dimensions in the two alternative tasks do not have to share the same representation nor need the stimuli of the two tasks have any feature in common. (PsycINFO Database Record (c) 2010 APA, all rights reserved)