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At least 1,207 records · Page 67Linked to original sources
PubMed2006

Striatal serotonin depletion facilitates rat egocentric learning via dopamine modulation.

Egocentric spatial learning has been defined as the ability to navigate in an environment using only proprioceptive information, thereby performing a motor response based on one's own movement. This form of learning has been associated with the neural memory system, including the striatum body. Cerebral serotonin depletion induces better performance, both in tasks with strong egocentric components and in egocentric navigation in the Morris' maze. Based on this, we propose that the striatal serotonergic depletion must facilitate egocentric learning. Fifteen female Sprague Dawley rats weighing 250-350 g and maintained under standard conditions were chronically implanted with infusion cannulas for bilateral application of drugs into the striatum. The animals were evaluated for egocentric navigation using the Morris' maze, under different conditions: saline solution infusion, serotonin depletion by infusion of 5,7-Dihydroxytryptamine (25 microg of free base solved in 2.5 microl of ascorbic acid 1% in saline solution), infusion of mixed dopamine D(1) and D(2) receptor antagonists (0.5 microl/min during 5 min of mixed spiperone 20 microM and SCH23390 10 microM), or serotonin depletion and dopamine blockade simultaneously. Striatal serotonin depletion facilitated egocentric learning, which was demonstrated as shorter escape latencies and the display of a defined sequence of movements for reaching the platform. The facilitation was not observed under condition of simultaneous dopamine blockade. Striatal serotonin depletion produced a dopamine-dependent facilitation of egocentric learning. A role for serotonin in the inhibition of striatal-mediated learning strategies is proposed.

5,7-Dihydroxytryptamine↗
PubMed1995

Clonidine and diazepam have differential effects on tests of attention and learning.

The noradrenergic system has repeatedly been implicated in the mediation of attentional processes. Using a double-blind, placebo-controlled design, the present investigation examines the effects of two doses (1.5 micrograms/kg and 2.5 micrograms/kg) of the alpha 2 adrenoceptor agonist clonidine (CLO) on performance of various computerised tests of attention and learning in healthy, young volunteers. These are compared to the effects produced by two doses (5 mg and 10 mg) of diazepam (DZP) on largely the same set of neuropsychological tests in a comparable set of subjects. Both doses of CLO were found to impair performance of the RVIP test of sustained attention, while the higher dose alone improved visuo-spatial learning. Conversely, the higher dose of DZP produced profound deficits on visuo-spatial learning, and impaired attentional set-shifting. This study suggests a role for the alpha 2 adrenoceptor in selective attention, and for the benzodiazepine receptor in specific cognitive processes mediated by discrete cortical regions.

Adult↗
PubMed1998

Spatial and discrimination learning in rodents infected with the nematode Strongyloides ratti.

Recent work has shown that mice with subclinical parasitic infections suffer impaired spatial learning and memory, as assayed in an open-field water maze. Although the mechanism underlying this effect is not clear, the phenomenon has been reported following infection with both a protozoan parasite (Eimeria vermiformis) and a gastrointestinal nematode (Heligmosomoides polygyrus). In a variety of experiments, we examined the effects of a different gastrointestinal nematode, Strongyloides ratti, on the ability of rats and mice to learn a spatial or a discrimination task. Animals were tested at various stages post-infection, with different levels of infection, using different lines of S. ratti and with varying experimental protocols. All animals learned the tasks, but we found no evidence of an effect of S. ratti infection on learning or memory. Even rats infected with approximately 5000 S. ratti larvae, a dose which has an impact on rat body size, showed no deficit in learning ability. Various reasons for the conflict between our results and those previously reported for E. vermiformis and H. polygyrus are discussed. Our results show that impaired learning and memory following parasitic infection is not a ubiquitous or at least easily replicated phenomenon.

Analysis of Variance↗
PubMedDate not supplied

Impaired learning and motor behavior in heterozygous Pafah1b1 (Lis1) mutant mice.

Heterozygous mutation or deletion of Pafab1b1 (LIS1) in humans is associated with syndromes with type 1 lissencephaly, a severe brain developmental disorder resulting from abnormal neuronal migration. We have created Lis1 heterozygous mutant mice by gene targeting. Heterozygous mutant mice are viable and fertile, but display global organizational brain defects as a result of impaired neuronal migration. To assess the functional impact of the mutation, Lis1 heterozygous mice and their wild-type littermates were evaluated on a wide variety of behavioral tests. Lis1 mutant mice displayed abnormal hindpaw clutching responses and were impaired on a rotarod test. Lis1 heterozygous mice were also impaired in the spatial learning version of the Morris water task. Impaired motor behavior and spatial learning and memory in Lis1 mutant mice indicates that impaired neuronal migration can have functional effects on complex behavioral responses. The behavioral findings also support the use of the Lis1 mutant mice as a model from human type 1 lissencephaly.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2005

Parathyroidectomy improves neurocognitive deficits in patients with primary hyperparathyroidism.

BACKGROUND: Clinical guidelines for the treatment of primary hyperparathyroidism (pHPT) often suggest parathyroidectomy, but generally fail to consider neurocognitive and psychiatric symptoms because of the relative paucity of evidence. METHODS: In this prospective study, patients with pHPT (PTX) and benign euthyroid thyroid disease (THY) referred for operation were evaluated pre- and postoperatively with validated psychometric and neurocognitive instruments to determine whether learning, memory, or concentration improved with after parathyroidectomy. Statistical comparisons between groups were performed with univariate analysis and repeated measures of analysis of variance. RESULTS: Fifty-five subjects, mean age of 54 years, were evaluated preoperatively; 41 returned postoperatively. There were no significant differences between groups by age and gender. PTXs reported more depression symptoms preoperatively (P = .04) that improved postoperatively. There were no differences between the 2 groups on verbal memory and trait anxiety. For PTXs, average preoperative serum calcium concentration (11.3 mg/dL) and serum PTH level (100 pg/mL) normalized postoperatively. Preoperatively PTXs showed greater delays in their spatial learning (P = .03). All subjects learned across the 5 trials, but PTXs were more delayed (P = .03). After operation, PTXs improved and functioned at a level equivalent to the THYs. There was an interaction between trial (neurocognitive testing), visit (pre- vs postoperative), status (PTX vs THY), and change in PTH level (P = .06), suggesting that individuals with greater change in PTH were more likely to improve in their learning efficiency postparathyroidectomy. CONCLUSIONS: PHPT may be associated with a spatial learning deficit and processing that improves after parathyroidectomy. While longer-term follow-up is necessary, neurocognitive symptoms perhaps should be considered as criteria for parathyroidectomy.

Adult↗
PubMed1997

Perceptual learning of spatial localization: specificity for orientation, position, and context.

Discrimination of simple visual attributes can improve significantly with practice. We have trained human observers to perform peripherally presented tasks involving the localization of short line segments and examined the specificity of the learning for the visual location, orientation, and geometric arrangement of the trained stimulus. Several weeks of training resulted in dramatic threshold reductions. The learning was specific for the orientation and location of the trained stimulus, indicating the involvement of the earliest cortical stages in the visual pathway where the orientation and location of stimuli are mapped with highest resolution. Furthermore, improvement was also specific for both the configuration of the trained stimulus and the attribute of the stimulus that was under scrutiny during training. This degree of specificity suggests that the learning cannot be achieved by cortical recruitment alone, as proposed in current models, but is likely to involve a refinement of lateral interactions within the cortex and possibly a gating of lower level changes by attentional mechanisms.

Cues↗
PubMed2006

The stamp of ancestry: roots of behavioral and neuronal impairment in adulthood.

Exposure of pregnant animals to noxious conditions affects neuronal function in the offspring. However, exposure or treatment of the maternal animal during pregnancy affects both ancestor and offspring. In the present study, female CD-1 mice were repetitively treated with 3-nitropropionate (3-np), a selective inhibitor of succinic dehydrogenase, exclusively prior to mating. Clinically, mice appeared normal during treatment. Five days after cessation of treatment animals were mated with control male animals. At 4 months of age spatial learning, LTP, NADH autofluorescence, and hypoxic tolerance were alike in controls and the offspring of treated female ancestors. However, an additional metabolic challenge in the offspring unmasks impairment of spatial learning, diminution of long-term potentiation (LTP), an altered protein microenvironment of mitochondrial enzymes, and reduced hypoxic tolerance. We conclude that the exposure of maternal ancestors to subclinical repetitive impairment of oxidative phosphorylation fosters impairment of behavior and neuronal function in the adult offspring, becoming apparent only on additional challenge. This finding may ultimately help to understand the causes of neuronal impairment or even neuropsychiatric disease in old age.

Age Factors↗
PubMed2005

Impaired water maze navigation of Wistar rats with retrosplenial cortex lesions: effect of nonspatial pretraining.

Damage to the retrosplenial cortex (RC) impairs the performance of rodents on spatial learning and memory tasks, but the extent of these deficits was previously reported to be influenced by the lesion type, rat strain, and behavioral task used. The present study addressed the issue of whether or not cytotoxic damage to RC impairs place navigation of Wistar rats in the Morris water maze and, if so, whether this is merely attributable to spatial learning deficits or to impaired learning of general (nonspatial) behavioral strategies required to correctly perform this task or both. Behaviorally naive rats with bilateral lesions to RC were significantly impaired relative to sham-lesioned rats both during the period of initial learning of the task and during the later phases of training. In addition, these animals showed enhanced thigmotaxis, indicating that the lesion was associated with considerable abnormalities in nonspatial learning. In contrast, RC-lesioned animals that have been previously familiarized with general task rules in a series of shaping trials did not show more thigmotaxis than did their respective controls. Furthermore, although these rats were still impaired in the middle of the training process, their performance during the period of initial learning as well as by the end of training was found to now be normal. Our results confirm those of earlier studies indicating that RC is important for spatial navigation. The findings herein reported are also consistent with the notion that, in addition to spatial information processing, RC is involved in cognitive processes underlying the ability of subjects to properly respond to general task demands.

Analysis of Variance↗
PubMed2001

Maternal deprivation increases 5-HT(1A) receptor expression in the CA1 and CA3 areas of senescent Brown Norway rats.

Maternally-deprived male Brown Norway rats were classified as non-impaired or impaired according to their performance in the water maze when 3 and 30-32 months old. Age and spatial learning ability did not affect the pattern and density of hippocampal 5-HT(1A)-receptor mRNA in mother-reared control rats. However, senescent maternally-deprived rats with impaired spatial learning ability showed increased expression of 5-HT(1A)-receptor mRNA in the hippocampal CA1 (14%) and CA3 (13%) areas but not in the dentate gyrus.

Adrenal Cortex Hormones↗
PubMed2001

Dorsal/ventral hippocampus, fornix, and conditioned place preference.

Conditioned place preference (CPP) is a learning paradigm requiring formation of associations between reward and particular locations. White and McDonald (Behav Brain Res 1993;55:269-281) demonstrated that amygdala (AMG) lesions impair, while fornix (Fx) lesions enhance learning of this task. In the present experiments, we replicated the effects of AMG and Fx lesions, but we also found that complete hippocampal (HPC) lesions interfere with normal performance. Thus, the effects of Fx and HPC lesions on CPP are opposite. This is in contrast with spatial learning in the water maze. Because it has been demonstrated that damage of dorsal HPC interferes to a greater extent with spatial learning than damage of ventral HPC, we also tested animals with either dorsal or ventral HPC disruptions on CPP. Lesions limited to dorsal HPC were followed by impairment on this task. In contrast, lesions limited to ventral HPC resulted in enhanced learning. We argue that Fx and HPC lesions do not have interchangeable effects in all learning paradigms. To explain the complex pattern of results presently obtained, we propose a novel hypothesis regarding behavioral functions of HPC neural circuits. Implications regarding the interaction between memory systems are also considered.

Animals↗
PubMedDate not supplied

Red ginseng ameliorated place navigation deficits in young rats with hippocampal lesions and aged rats.

Effects of hippocampal lesions and aging on spatial learning and memory and ameliorating effects of red ginseng on learning deficits were investigated in the following two experiments: performance of young rats with selective hippocampal lesions with red ginseng by mouth (p.o.; Experiment 1) and aged rats with red ginseng (p.o.; Experiment 2) in the spatial tasks was compared with that of sham-operated or intact young rats. Each rat in these two behavioral experiments was tested with the three types of spatial-learning tasks (distance movement task, DMT; random-reward place search task, RRPST; and place-learning task, PLT) in a circular open field using intracranial self-stimulation as reward. The results in the DMT and RRPST tasks indicated that motivational and motor activity of young rats with hippocampal lesions with and without ginseng were not significantly different from that of sham-operated young rats in Experiment 1. However, young rats with hippocampal lesions displayed significant deficits in the PLT task. Treatment with red ginseng significantly ameliorated place-navigation deficits in young rats with hippocampal lesions on the PLT task. Similarly, red ginseng improved performance of aged rats on the PLT task in Experiment 2. The results, along with previous studies showing significant effects of red ginseng on the central nervous system, suggest that red ginseng ameliorates learning and memory deficits through effects on the central nervous system, partly through effects on the hippocampal formation.

Aging↗
PubMed1987

Chlordiazepoxide, an anxiolytic benzodiazepine, impairs place navigation in rats.

There are separate proposals that the hippocampus is involved in 'spatial memory' and in the control of 'anxiety'. Despite a larger number of common effects of anxiolytic drugs and hippocampal lesions, no effect of anxiolytic drugs has yet been reported in those spatial tasks which are particularly sensitive to the effects of hippocampal lesions. The present study addresses this issue. Separate groups of rats were treated, i.p., with 5 mg/kg chlordiazepoxide (an anxiolytic benzodiazepine), 1 mg/kg scopolamine (a muscarinic antagonist which has previously been shown to impair spatial learning) and a saline placebo. They were then trained to find a platform which was hidden in a constant location just under the surface of opaque water in a swimming pool. Separate groups of rats were trained with 4 trials per day and with 1 trial per day. Number of trials per day did not significantly influence the effects of the drugs. Chlordiazepoxide and scopolamine produced similar degrees of impairment in spatial learning to each other--but less impairment than has previously been reported with hippocampal lesions. The effectiveness of the anxiolytic drug chlordiazepoxide in the swimming pool, a specifically spatial task, suggests that the opposing concepts of 'spatial memory' and 'anxiety' which have been used previously to describe hippocampal function may represent different aspects of a unitary concept.

Animals↗
PubMed1997

Examining the right temporal lobe's role in nonverbal memory.

Tests of facial recognition and spatial learning were administered to presurgical patients with unilateral temporal lobe EEG foci. Right temporal lobe patients obtained lower facial recognition scores than left temporal lobe patients. The groups performed equally on the spatial learning test. A factor analysis revealed two independent factors: a general visuospatial factor and a more specific facial identification factor. The findings provide support for the existence of two dissociable visual processing systems. Memory impairments associated with right temporal lobe dysfunction may be characterized as an impairment in a ventral visual processing system responsible for facial memory and pattern recognition.

Adolescent↗
PubMed2000

Repeated ECS and fluoxetine administration have equivalent effects on hippocampal synaptic plasticity.

RATIONALE: Recent studies have implicated intracellular transduction pathways and neurotrophic factors in the action of antidepressants. Adaptation in these pathways may ultimately affect electrophysiological and morphological properties of neurones. We have previously shown that repeated electroconvulsive stimulation, a safe and effective antidepressant treatment, has profound effects on hippocampal synaptic connectivity and plasticity in the rat. Here, we investigated whether these electrophysiological properties were shared by the chemical antidepressant, fluoxetine. OBJECTIVES: To compare the electrophysiological and cognitive effects of two very different antidepressant treatments: repeated electroconvulsive stimulation (rECS); and chronic administration of the serotonin specific re-uptake inhibitor (SSRI), fluoxetine. METHODS: Rats were exposed to either rECS or daily fluoxetine administration for 15 days. The animals were then anaesthetised and dentate field excitatory post-synaptic potential (fEPSP) characteristics were measured before and after the induction of long-term potentiation (LTP) by high frequency perforant path stimulation. In a separate experiment, the effects of rECS and chronic fluoxetine administration on acquisition and retention of a spatial learning task in the Morris watermaze were determined. RESULTS: Chronic fluoxetine administration and rECS produced equivalent increases in dentate fEPSP compared to respective control groups. LTP induction was attenuated in both groups. Spatial learning was, in contrast, unaffected by fluoxetine treatment but significantly impaired following rECS. CONCLUSIONS: Given that fluoxetine and rECS share antidepressant properties, but differ in their effects on learning and memory, we propose that the common effects on dentate connectivity and synaptic plasticity described here are more likely to relate to affective rather than cognitive function. This result is consistent with other experiments showing that a reduction in dentate connectivity correlates with stress susceptibility in animals.

Animals↗
PubMed1999

Long-term deprivation of oestrogens by ovariectomy potentiates beta-amyloid-induced working memory deficits in rats.

1 In the present study, we examined whether deprivation of oestrogens by ovariectomy could modify learning and memory deficits caused by a continuous intracerebroventricular (i.c.v.) infusion of amyloid beta-peptide (Abeta), the major constituent of senile plaques in AD. 2 Neither long-term (3 months) nor short-term (1 month), deprivation of oestrogens by ovariectomy caused a significant impairment in spatial learning and memory in a water maze and spontaneous alternation behaviour in a Y-maze. 3 A continuous i.c.v. infusion of Abeta-(1-42) caused spatial learning and memory deficits in both ovariectomized and sham-operated rats. 4 The Abeta-induced working memory deficits were significantly potentiated in ovariectomized rats compared with sham-operated rats when mnemonic ability was examined 3 months after ovariectomy. 5 These results suggest that long-term deprivation of oestrogens induced by ovariectomy increases susceptibility to memory deficits produced by Abeta-(1-42) in rats.

Amyloid beta-Peptides↗
PubMed1991

Transgenic mice for the amyloid precursor protein 695 isoform have impaired spatial memory.

Transgenic mice for the human amyloid precursor protein 695 (APP695) isoform may provide an animal model of Alzheimer's disease (AD). To evaluate this, the spatial learning abilities of transgenic and wild strain mice were compared in the Morris water maze task. The transgenic mice were significantly retarded in initial learning and in learning a new escape location, although in each case they eventually reached control levels. The transgenic mice also showed slower swimming speed and reduced nocturnal activity, which may contribute to their deficit in spatial learning. Preliminary neuropathological investigations failed to reveal amyloid depositions. Thus, a gene dosage effect of APP695 may account for the memory impairment but not the plaque formation associated with AD.

Amyloid beta-Peptides↗
PubMed2006

NAP enhances neurodevelopment of newborn apolipoprotein E-deficient mice subjected to hypoxia.

Perinatal hypoxic injury is associated with significant neonatal morbidity and long-term neurodevelopmental complications. NAP, a peptide derived from ADNP (activity-dependent neuroprotective protein), has previously shown neuroprotective abilities in various adult animal models. To evaluate its neuroprotective role in neonatal hypoxic-ischemic injury, we evaluated the neurodevelopmental outcome in apolipoprotein E (ApoE)-deficient (knockout) mice (a breed prone to brain damage during hypoxic insult) exposed to postnatal global hypoxic damage with and without treatment with NAP. ApoE-deficient (n = 80) and control (C57B6) mice pups (n = 81) were exposed to postnatal global hypoxia (35 min of 8% O(2) within 24 h of birth) or room air with or without subsequent subcutaneous NAP treatment during postnatal days 1 to 14. Pups were then evaluated for neonatal motor reflex attainment, spatial learning ability in the Morris water maze, and locomotor open-field activity. The C57B6 and ApoE-deficient anoxic groups showed significantly slower achievement of neonatal reflexes, diminished locomotor activity, and diminished spatial learning ability compared with their control groups. This was more pronounced in the anoxic ApoE-deficient pups. NAP treatment had a pronounced effect on neurodevelopmental outcome in both breeds, particularly in the ApoE-deficient mice. ApoE-deficient and control mouse pups exposed to postnatal hypoxia and treated with NAP showed improvement in neurodevelopmental outcome compared with nontreated mice pups. ApoE-deficient mice show a greater susceptibility to hypoxic damage and better response to NAP treatment.

Animals↗
PubMed2000

Environmental enrichment from birth enhances visual acuity but not place learning in mice.

The effect of richness of the environment on behavioral function was investigated in C57B6 mice. Animals were raised in either enriched (group-housed in large clear plexiglas cages with stimulating objects) or restricted (group housed in opaque white plastic cages with no stimulating objects) environmental conditions and their spatial learning and visual acuity were measured as adults. The performance of enriched and restricted groups were indistinguishable in place and cued versions of the Morris water task; however, the visual acuity of the enriched group, measured in a grating versus gray version of the visual water task, was 18% higher than the restricted group. These data demonstrate that the function of the mouse visual system can be significantly influenced by the nature of early visual input. They also indicate that the effects of environmental enrichment are manifested differently in behavioral measures of spatial learning and visual acuity.

Animals↗