			Home About us Contact

Learning Deficits (learning + deficit)

Distribution by Scientific Domains

Medical Sciences	58%
Life Sciences	29%

Selected Abstracts

Effects of a Novel Cognition-Enhancing Agent on Fetal Ethanol-Induced Learning Deficits

ALCOHOLISM, Issue 10 2010
Daniel D. Savage
Background:, Drinking during pregnancy has been associated with learning disabilities in affected offspring. At present, there are no clinically effective pharmacotherapeutic interventions for these learning deficits. Here, we examined the effects of ABT-239, a histamine H3 receptor antagonist, on fetal ethanol-induced fear conditioning and spatial memory deficits. Methods and Results:, Long-Evans rat dams stably consumed a mean of 2.82 g ethanol/kg during a 4-hour period each day during pregnancy. This voluntary drinking pattern produced a mean peak serum ethanol level of 84 mg/dl. Maternal weight gain, litter size and birth weights were not different between the ethanol-consuming and control groups. Female adult offspring from the control and fetal alcohol-exposed (FAE) groups received saline or 1 mg ABT-239/kg 30 minutes prior to fear conditioning training. Three days later, freezing time to the context was significantly reduced in saline-treated FAE rats compared to control. Freezing time in ABT-239-treated FAE rats was not different than that in controls. In the spatial navigation study, adult male offspring received a single injection of saline or ABT-239 30 minutes prior to 12 training trials on a fixed platform version of the Morris Water Task. All rats reached the same performance asymptote on Trials 9 to 12 on Day 1. However, 4 days later, first-trial retention of platform location was significantly worse in the saline-treated FAE rats compared control offspring. Retention by ABT-239-treated FAE rats was similar to that by controls. ABT-239's effect on spatial memory retention in FAE rats was dose dependent. Conclusions:, These results suggest that ABT-239 administered prior to training can improve retention of acquired information by FAE offspring on more challenging versions of hippocampal-sensitive learning tasks. Further, the differential effects of ABT-239 in FAE offspring compared to controls raises questions about the impact of fetal ethanol exposure on histaminergic neurotransmission in affected offspring. [source]

Developmental dyslexia and explicit long-term memory

DYSLEXIA, Issue 3 2010
Deny Menghini
Abstract The reduced verbal long-term memory capacities often reported in dyslexics are generally interpreted as a consequence of their deficit in phonological coding. The present study was aimed at evaluating whether the learning deficit exhibited by dyslexics was restricted only to the verbal component of the long-term memory abilities or also involved visual-object and visual-spatial domain. A further goal of the present study was to investigate the predictive value of non-verbal long-term memory abilities with respect to word and non-word reading in dyslexic children. In accordance with these aims, performances of 60 dyslexic children were compared with that of 65 age-matched normal readers on verbal, visual-spatial and visual-object task. Results documented a generalized impairment of episodic long-term memory capacities in dyslexic children and the results did not vary as a function of children's age. Furthermore, in addition to verbal measures, also individual differences in non-verbal long-term memory tasks turn out to be good predictors of reading difficulties in dyslexics. Our findings indicate that the long-term memory deficit in dyslexia is not limited to the dysfunction of phonological components but also involves visual-object and visual-spatial aspect, thus suggesting that dyslexia is associated to multiple cognitive deficits. Copyright © 2010 John Wiley & Sons, Ltd. [source]

Enhancement of learning behaviour by a potent nitric oxide-guanylate cyclase activator YC-1

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2005
Wei-Lin Chien
Abstract Memory is one of the most fundamental mental processes, and various approaches have been used to understand the mechanisms underlying this process. Nitric oxide (NO), cGMP and protein kinase G (PKG) are involved in the modulation of synaptic plasticity in various brain regions. YC-1, which is a benzylindazole derivative, greatly potentiated the response of soluble guanylate cyclase to NO (up to several hundreds fold). We have previously shown that YC-1 markedly enhances long-term potentiation in hippocampal and amygdala slices via NO-cGMP-PKG-dependent pathway. We here further investigated whether YC-1 promotes learning behaviour in Morris water maze and avoidance tests. It was found that YC-1 shortened the escape latency in the task of water maze, increased and decreased the retention scores in passive and active avoidance task, respectively. Administration of YC-1 30 min after foot-shock stimulation did not significantly affect retention scores in response to passive avoidance test. Administration of scopolamine, a muscarinic antagonist, markedly impaired the memory acquisition. Pretreatment of YC-1 inhibited the scopolamine-induced learning deficit. The enhancement of learning behaviour by YC-1 was antagonized by intracerebroventricular injection of NOS inhibitor L-NAME and PKG inhibitors of KT5823 and Rp-8-Br-PET-cGMPS, indicating that NO-cGMP-PKG pathway is also involved in the learning enhancement action of YC-1. YC-1 is thus a good drug candidate for the improvement of learning and memory. [source]

Impaired long-term depression in P2X3 deficient mice is not associated with a spatial learning deficit

JOURNAL OF NEUROCHEMISTRY, Issue 5 2006
Yue Wang
Abstract The hippocampus is a brain region critical for learning and memory processes believed to result from long-lasting changes in the function and structure of synapses. Recent findings suggest that ATP functions as a neurotransmitter or neuromodulator in the mammalian brain, where it activates several different types of ionotropic and G protein-coupled ATP receptors that transduce calcium signals. However, the roles of specific ATP receptors in synaptic plasticity have not been established. Here we show that mice lacking the P2X3 ATP receptor (P2X3KO mice) exhibit abnormalities in hippocampal synaptic plasticity that can be restored by pharmacological modification of calcium-sensitive kinase and phosphatase activities. Calcium imaging studies revealed an attenuated calcium response to ATP in hippocampal neurons from P2X3KO mice. Basal synaptic transmission, paired-pulse facilitation and long-term potentiation are normal at synapses in hippocampal slices from P2X3KO. However, long-term depression is severely impaired at CA1, CA3 and dentate gyrus synapses. Long-term depression can be partially rescued in slices treated with a protein phosphatase 1,2 A activator or by postsynaptic inhibition of calcium/calmodulin-dependent protein kinase II. Despite the deficit in hippocampal long-term depression, P2X3KO mice performed normally in water maze tests of spatial learning, suggesting that long-term depression is not critical for this type of hippocampus-dependent learning and memory. [source]

Pharmacological effects of carcinine on histaminergic neurons in the brain

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2004
Zhong Chen
Carcinine (, -alanyl histamine) is an imidazole dipeptide. The present study was designed to characterize the pharmacological effects of carcinine on histaminergic activity in the brain and on certain neurobehavior. Carcinine was highly selective for the histamine H3 receptor over H1 or H2 receptor (Ki (,M)=0.2939±0.2188 vs 3621.2±583.9 or 365.3±232.8 ,M, respectively). Carcinine at a dose of 20 mg kg,1 slightly increased histidine decarboxylase (HDC) activity in the cortex (from 0.186±0.069 to 0.227±0.009 pmol mg protein,1 min,1). In addition, carcinine (10, 20, and 50 mg kg,1) significantly decreased histamine levels in mice brain. Like thioperamide, a histamine H3 receptor antagonist, carcinine (20, 50 ,M) significantly increased 5-HT release from mice cortex slices, but had no apparent effect on dopamine release. Carcinine (20 mg kg,1) significantly inhibited pentylenetetrazole-induced kindling. This inhibition was completedly reversed by (R)- , -methylhistamine, a representative H3 receptor agonist, and , -fluromethylhistidine, a selective HDC inhibitor. Carcinine (20 mg kg,1) ameliorated the learning deficit induced by scopolamine. This amelioration was reversed by (R)- , -methylhistamine as evaluated by the passive avoidance test in mice. Like thioperamide, carcinine dose-dependently increased mice locomotor activity in the open-field test. The results of this study provide first and direct evidence that carcinine, as a novel histamine H3 receptor antagonist, plays an important role in histaminergic neurons activation and might be useful in the treatment of certain diseases, such as epilepsy, and locomotor or cognitive deficit. British Journal of Pharmacology (2004) 143, 573,580. doi:10.1038/sj.bjp.0705978 [source]

Investigating learning deficits associated with dyslexia

DYSLEXIA, Issue 1 2004
Emmanuel M. Pothos
Abstract An artificial grammar learning task was used to define two learning tasks of identical complexity at the symbolic level, but which differed in terms of stimulus format. The stimuli in one learning task were created so as to encourage participants to perceive each stimulus as a whole, with less emphasis on the stimulus constituent elements (the ,embedded' stimuli), while in the second task the constituent elements of each stimulus were emphasized by presenting them serially (the ,sequences' stimuli). Using a between participants design, dyslexic participants performed equally well in the two versions of the learning task. By contrast, non-dyslexic participants performed as well as dyslexic ones with the embedded stimuli but were impaired in the sequences stimuli. This finding was interpreted as showing that dyslexic participants were less able, compared to controls, to process individual stimulus elements of both the sequences and the embedded stimuli, consistently with recent work associating dyslexia with problems in attention focusing and shifting. Copyright © 2004 John Wiley & Sons, Ltd. [source]

Open-field Behaviors and Water-maze Learning in the F Substrain of Ihara Epileptic Rats

EPILEPSIA, Issue 1 2006
Yoko Okaichi
Summary:,Purpose: Genetically epileptic model rats, Ihara epileptic rat (IER/F substrain), have neuropathologic abnormalities and develop generalized convulsive seizures when they reach the age of ,5 months. Because the neuromorphologic abnormalities are centered in the hippocampus, we expected to observe spatial cognitive deficits. The present study aimed to evaluate emotionality and learning ability of the F substrain of IER. Methods: To determine whether deficits are caused by inborn neuropathologic abnormalities or by repeated generalized convulsions, we tested nine 6- to 12-week-old IER/F rats that had not yet experienced seizures (experiment 1) and nine 7- to 9-month-old IER/F rats that had repeatedly experienced seizures (experiment 2) with identical tasks: an open-field test and the Morris water-maze place and cue tasks. Results: Both groups of IER/Fs showed behaviors that were different from those of control rats in the open-field test, and extensive learning impairments were seen in both the place task, which requires spatial cognition, and the cue task, which does not require spatial cognition but requires simple association learning. Their impaired performance of the cue task indicates that their deficiency was not limited to spatial cognition. Conclusions: Because young IER/F rats without seizure experiences also showed severe learning impairments, genetically programmed microdysgenesis in the hippocampus was suspected as a cause of the severe learning deficits of IER/Fs. [source]

The impact of mineralocorticoid receptor ISO/VAL genotype (rs5522) and stress on reward learning

GENES, BRAIN AND BEHAVIOR, Issue 6 2010
R. Bogdan
Research suggests that stress disrupts reinforcement learning and induces anhedonia. The mineralocorticoid receptor (MR) determines the sensitivity of the stress response, and the missense iso/val polymorphism (Ile180Val, rs5522) of the MR gene (NR3C2) has been associated with enhanced physiological stress responses, elevated depressive symptoms and reduced cortisol-induced MR gene expression. The goal of these studies was to evaluate whether rs5522 genotype and stress independently and interactively influence reward learning. In study 1, participants (n = 174) completed a probabilistic reward task under baseline (i.e. no-stress) conditions. In study 2, participants (n = 53) completed the task during a stress (threat-of-shock) and no-stress condition. Reward learning, i.e. the ability to modulate behavior as a function of reinforcement history, was the main variable of interest. In study 1, in which participants were evaluated under no-stress conditions, reward learning was enhanced in val carriers. In study 2, participants developed a weaker response bias toward a more frequently rewarded stimulus under the stress relative to no-stress condition. Critically, stress-induced reward learning deficits were largest in val carriers. Although preliminary and in need of replication due to small sample size, findings indicate that psychiatrically healthy individuals carrying the MR val allele, gene, which has been recently linked to depression, showed a reduced ability to modulate behavior as a function of reward when facing an acute, uncontrollable stressor. Future studies are warranted to evaluate whether rs5522 genotype interacts with naturalistic stressors to increase the risk of depression and whether stress-induced anhedonia might moderate such risk. [source]

Genetic variation in brain-derived neurotrophic factor and human fear conditioning

GENES, BRAIN AND BEHAVIOR, Issue 1 2009
G. Hajcak
Brain-derived neurotrophic factor (BDNF) has been implicated in hippocampal-dependent learning processes, and carriers of the Met allele of the Val66Met BDNF genotype are characterized by reduced hippocampal structure and function. Recent nonhuman animal work suggests that BDNF is also crucial for amygdala-dependent associative learning. The present study sought to examine fear conditioning as a function of the BDNF polymorphism. Fifty-seven participants were genotyped for the BDNF polymorphism and took part in a differential-conditioning paradigm. Participants were shocked following a particular conditioned stimulus (CS+) and were also presented with stimuli that ranged in perceptual similarity to the CS+ (20, 40 or 60% smaller or larger than the CS+). The eye blink component of the startle response was measured to quantify fear conditioning; post-task shock likelihood ratings for each stimulus were also obtained. All participants reported that shock likelihood varied with perceptual similarity to the CS+ and showed potentiated startle in response to CS ± 20% stimuli. However, only the Val/Val group had potentiated startle responses to the CS+. Met allele carrying individuals were characterized by deficient fear conditioning , evidenced by an attenuated startle response to CS+ stimuli. Variation in the BDNF genotype appears related to abnormal fear conditioning, consistent with nonhuman animal work on the importance of BDNF in amygdala-dependent associative learning. The relation between genetic variation in BDNF and amygdala-dependent associative learning deficits is discussed in terms of potential mechanisms of risk for psychopathology. [source]

Temperature affects longevity and age-related locomotor and cognitive decay in the short-lived fish Nothobranchius furzeri

AGING CELL, Issue 3 2006
Dario R. Valenzano
Summary Temperature variations are known to modulate aging and life-history traits in poikilotherms as different as worms, flies and fish. In invertebrates, temperature affects lifespan by modulating the slope of age-dependent acceleration in death rate, which is thought to reflect the rate of age-related damage accumulation. Here, we studied the effects of temperature on aging kinetics, aging-related behavioural deficits, and age-associated histological markers of senescence in the short-lived fish Nothobranchius furzeri. This species shows a maximum captive lifespan of only 3 months, which is tied with acceleration in growth and expression of aging biomarkers. These biological peculiarities make it a very convenient animal model for testing the effects of experimental manipulations on life-history traits in vertebrates. Here, we show that (i) lowering temperature from 25 °C to 22 °C increases both median and maximum lifespan; (ii) life extension is due to reduction in the slope of the age-dependent acceleration in death rate; (iii) lowering temperature from 25 °C to 22 °C retards the onset of age-related locomotor and learning deficits; and (iv) lowering temperature from 25 °C to 22 °C reduces the accumulation of the age-related marker lipofuscin. We conclude that lowering water temperature is a simple experimental manipulation which retards the rate of age-related damage accumulation in this short-lived species. [source]

The orally combined neuroprotective effects of sodium ferulate and borneol against transient global ischaemia in C57 BL/6J mice

JOURNAL OF PHARMACY AND PHARMACOLOGY: AN INTERNATI ONAL JOURNAL OF PHARMACEUTICAL SCIENCE, Issue 7 2010
Xiao-hong Chen
Abstract Objectives, This study aimed to investigate the possible modification of the neuroprotective effect of sodium ferulate, when orally co-administered with borneol, in transient global cerebral ischaemia-induced functional, histological and cellular alterations in mice. Methods, The bilateral common carotid artery occlusion was conducted in C57 BL/6J mice for 25 min. The mice were then subjected to a water maze test over an extended recovery period, followed by an assessment of neuronal loss in the CA1 region of the hippocampus (haematoxylin and eosin staining). The blood,brain barrier permeability (Evans blue tracing), brain oedema and oxidative stress were assayed and histological sections were also immunostained for gliofibrillar acid protein (GFAP) expression. Key findings, The ischaemia reperfused mice were associated with long-lasting spatial learning deficits in the absence of other behavioural impairments and with neurodegeneration in the hippocampal CA1 region. However, the histological injuries were significantly attenuated by oral co-administration of sodium ferulate and borneol. Furthermore, combined treatment with sodium ferulate and borneol resulted in a significant reduction in brain oedema, GFAP-positive cells, malonaldialdehyde levels and blood,brain barrier permeability, but an increase in superoxide dismutase activity. Conclusions, Borneol may have benefits for the neuroprotective effect of sodium ferulate against injury induced in the brain by ischaemia/reperfusion. [source]

Effects of a Novel Cognition-Enhancing Agent on Fetal Ethanol-Induced Learning Deficits

A Mouse Model of Prenatal Ethanol Exposure Using a Voluntary Drinking Paradigm

ALCOHOLISM, Issue 12 2003
Andrea M. Allan
Background: The incidence of fetal alcohol spectrum disorders is estimated to be as high as 1 in 100 births. Efforts to better understand the basis of prenatal ethanol-induced impairments in brain functioning, and the mechanisms by which ethanol produces these defects, will rely on the use of animal models of fetal alcohol exposure (FAE). Methods: Using a saccharin-sweetened alcohol solution, we developed a free-choice, moderate alcohol access model of prenatal alcohol exposure. Stable drinking of a saccharin solution (0.066%) was established in female mice. Ethanol then was added to the saccharin in increasing concentrations (2%, 5%, 10% w/v) every 2 days. Water was always available, and mice consumed standard pellet chow. Control mice drank saccharin solution without ethanol. After a stable baseline of ethanol consumption (14 g/kg/day) was obtained, females were impregnated. Ethanol consumption continued throughout pregnancy and then was decreased to 0% in a step-wise fashion over a period of 6 days after pups were delivered. Characterization of the model included measurements of maternal drinking patterns, blood alcohol levels, food consumption, litter size, pup weight, pup retrieval times for the dams, and effects of FAE on performance in fear-conditioned learning and novelty exploration. Results: Maternal food consumption, maternal care, and litter size and number were all found to be similar for the alcohol-exposed and saccharin control animals. FAE did not alter locomotor activity in an open field but did increase the time spent inspecting a novel object introduced into the open field. FAE mice displayed reduced contextual fear when trained using a delay fear conditioning procedure. Conclusions: The mouse model should be a useful tool in testing hypotheses about the neural mechanisms underlying the learning deficits present in fetal alcohol spectrum disorders. Moreover, a mouse prenatal ethanol model should increase the opportunity to use the power of genetically defined and genetically altered mouse populations. [source]

Dose-Dependent Effects of Prenatal Ethanol Exposure on Synaptic Plasticity and Learning in Mature Offspring

ALCOHOLISM, Issue 11 2002
Daniel D. Savage
Background We have observed profound deficits in hippocampal synaptic plasticity and one-trial learning in offspring whose mothers drank moderate quantities of ethanol during pregnancy. In the present study, we examined the question of whether lower maternal blood ethanol concentrations (BECs) could produce functional deficits in offspring. Methods Rat dams consumed either a 2%, 3%, or 5% ethanol liquid diet throughout gestation. Three other groups of dams were pair-fed a 0% ethanol liquid diet, and a seventh group consumed lab chow ad libitum. Adult offspring from each diet group were assigned either to studies of evoked [3H]-D-aspartate (D-ASP) release from hippocampal slices or spatial learning studies using the Morris Water Task. Results Consumption of the 2%, 3%, and 5% ethanol liquid diets produced mean peak maternal BECs of 7, 30 and 83 mg/dL, respectively. Consumption of these ethanol diets had no effect on offspring birthweight, litter size or neonatal mortality. Likewise, evoked D-ASP release from hippocampal slices and performance on a standard version of the Morris Water Task were not affected by prenatal ethanol exposure. By contrast, activity-dependent potentiation of evoked D-ASP release from slices and one-trial learning on a "moving platform" version of the Morris Water Task were markedly reduced in offspring whose mothers consumed the 5% ethanol liquid diet. Intermediate deficits in these two parameters were observed in offspring from the 3% ethanol diet group, whereas offspring from the 2% ethanol diet group were not statistically different than controls. Conclusions We conclude that the threshold for eliciting subtle, yet significant learning deficits in offspring prenatally exposed to ethanol is less than 30 mg/dL. This BEC is roughly equivalent to drinking 1 to 1.5 ounces of ethanol per day. [source]

Cognitive deficits in Tsc1+/,mice in the absence of cerebral lesions and seizures

ANNALS OF NEUROLOGY, Issue 6 2007
Susanna M. I. Goorden MSc
Objective Tuberous sclerosis complex (TSC) is characterized by brain lesions, epilepsy, increased incidence of mental retardation and autism. The causal link between lesion load and epilepsy on cognitive disabilities has been debated, and these factors explain only part of the intelligence quotient variability. A Tsc2 rat model of the disease provided evidence that the TSC genes are directly involved in neuronal function. However, these lesion- and epilepsy-free animals did not show learning deficits, leaving open the possibility that the presence of brain lesions or epilepsy is a prerequisite for the cognitive deficits to fully develop. Here, we reinvestigated the relation among cerebral lesions, epilepsy, and cognitive function using Tsc1+/,mice. Methods We used immunocytochemistry and high-resolution magnetic resonance imaging to study the presence of neuronal pathology in Tsc1+/,mice. We used the Morris water maze, fear conditioning, social interaction, and nest building test to study the presence of cognitive and social deficits. Results We observed no spontaneous seizures or cerebral lesions in the brains of Tsc1+/,mice. In addition, giant dysmorphic cells were absent, and spine number and dendritic branching appeared to be normal. Nevertheless, Tsc1+/,mice showed impaired learning in the hippocampus-sensitive versions of the learning tasks and impaired social behavior. Interpretation Tsc1+/,mice show social and cognitive deficits in the absence of apparent cerebral pathology and spontaneous seizures. These findings support a model in which haploinsufficiency for the TSC genes leads to aberrations in neuronal functioning resulting in impaired learning and social behavior. Ann Neurol 2007 [source]

Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure

ANNALS OF NEUROLOGY, Issue 1 2003
Tomás R. Guilarte PhD
Long-term deficits in cognitive function are the principal effects of lead (Pb2+) exposure in children and can be modeled in experimental animals. Current therapeutic approaches in the treatment of childhood Pb2+ intoxication are not effective in reversing learning deficits once they have occurred. We report that environmental enrichment reverses long-term deficits in spatial learning produced by developmental Pb2+ exposure in rats. Enhanced learning performance of Pb2+ -exposed animals reared in an enriched environment was associated with recovery of deficits in N- methyl- D -aspartate receptor subunit 1 (NR1) mRNA and induction of brain-derived neurotrophic factor (BDNF) mRNA in the hippocampus. The effect of environmental enrichment on NR1 and BDNF gene expression was specific to Pb2+ -exposed animals and was present in the absence of changes in the NR2B subunit of the N- methyl- D -aspartate receptor, GluR1, ,CamKII, or PSD-95 gene expression measured in the same animals. Our findings demonstrate that the learning impairments and NR1 subunit mRNA deficits resulting from developmental Pb2+ exposure are reversible if the animals are provided with an enriched environment even after the exposure has occurred. We propose environmental enrichment as a basis for the treatment of childhood Pb2+ intoxication. [source]

Self-esteem in children with attention and/or learning deficits: the importance of gender

ACTA PAEDIATRICA, Issue 8 2008
Ulla Ek
Abstract Objective: Our objective was to analyze self-esteem in children within a spectrum of attention disorders, that is, besides attention deficit hyperactivity disorder (ADHD), also children with subthreshold ADHD and even milder attention deficits and/or learning problems. Methods: From a population-based group of 10,11-year-old children in a Swedish municipality those with ADHD/subthreshold ADHD (n = 30) and those with milder attention and/or learning problems (n = 64) were targeted for the study. The children completed the ,I think I am' scale, reflecting physical appearance, scholastic competence, mental well-being, relationships to parents and to others and global self-esteem. Data from boys and girls were compared and related to the parents' and teachers' ratings on the two dimensions of the Conners' 10-item questionnaire (impulsive-restless behaviour and emotional lability) and to the children's cognitive levels. Results: Significant gender differences were found, girls reporting lower self-esteem concerning mental well-being and poorer relationships with parents and peers. However, children with ADHD/subthreshold ADHD did not report significantly lower global self-esteem when compared to a reference population. Conclusion: Self-esteem in children with attention, behaviour and/or learning problems has to be carefully evaluated, especially in girls, and measures are needed to prevent a trajectory towards adolescent psychopathology. [source]