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PubMed2000

The effect of dopamine depletion from the caudate nucleus of the common marmoset (Callithrix jacchus) on tests of prefrontal cognitive function.

This study examined the effects of depletion of dopamine from the caudate nucleus of the common marmoset (Callithrix jacchus), on tasks sensitive to prefrontal damage (attentional set-shifting and spatial delayed response). There was a marked impairment in performance on the spatial delayed response task, but performance on the attentional set-shifting task was relatively preserved except for an impairment in re-engagement of a previously relevant perceptual dimension. This pattern of impairment is distinct from that seen after excitotoxic lesions of the prefrontal cortex and in patients with Parkinson's disease. Though it is not possible to identify specific cognitive functions that are independent of dopaminergic modulation of the caudate nucleus, due to the partial nature of the lesion, the results do provide insight into those cognitive processes that appear most dependent on caudate dopamine.

Animals↗
PubMedDate not supplied

Prenatal phenytoin exposure and spatial navigation in offspring: effects on reference and working memory and on discrimination learning.

Previous research has shown that rats exposed to phenytoin (PHT) in utero demonstrate abnormal circling, decreased learning, hyperactivity, and delayed air righting reflex development. The effects of prenatal PHT on offspring learning have been found on multiple-T mazes (Biel and Cincinnati types) and on spatial navigation (Morris maze). However, the specificity of the latter effects is unknown. Herein, we tested the effects of prenatal PHT in a Morris maze using six different procedures: cued versus spatial reference memory-based learning, cued versus spatial working memory-based learning, and cued versus spatial discrimination learning. PHT-exposed offspring showed increased preweaning mortality, growth reduction, and abnormal circling as noted in previous studies. PHT offspring were separated into those exhibiting circling and those not. PHT noncircling offspring demonstrated impaired reference memory-based spatial learning (acquisition and reversal), but no other effects. By contrast, PHT circling offspring demonstrated not only impaired reference memory-based spatial learning, but also impaired cued platform learning, impaired spatial discrimination, and impaired working memory-based learning. These data confirm that prenatal PHT induces a specific reference memory-based spatial learning deficit even in asymptomatic (noncircling) offspring that is distinct from the impairment induced in littermates exhibiting the circling impairment.

Analysis of Variance↗
PubMed1982

Learning ability of orphan foals, of normal foals and of their mothers.

The maze learning ability of six pony foals that had been weaned at birth was compared to that of six foals reared normally. The foals' learning ability was also compared to their mothers' learning ability at the same task; the correct turn in a single choice point maze. The maze learning test was conducted when the foals were 6 to 8 mo old and after the mothered foals had been weaned. There was no significant difference between the ability of orphaned (weaned at birth) and mothered foals in their ability to learn to turn left (6 +/- .7 and 5.1 +/- .1 trials, respectively) or to learn the reversal, to turn right (6.7 +/- .6 and 6.2 +/- .6 trials, respectively). The orphan foals spent significantly more time in the maze in their first exposure to it than the mothered foals (184 +/- 42 vs 55 +/- 15 s. Mann Whitney U = 7, P less than .05). The mothers of the foals (n = 11) learned to turn left as rapidly as the foals (5.9 +/- .7 trials), but they were slower to learn to turn right (9.8 +/- 1.4 vs 6.4 +/- .4 trials, Mann Whitney U = 33, P less than .05), indicating that the younger horses learned more rapidly. There was no correlation between the trials to criteria of the mare and those of her foal, but there was a significant negative correlation between rank in trials to criteria and age (r = -65, P less than .05) when data from the mare and foal trials were combined. The dominance hierarchy of the mares was determined using a paired feeding test in which two horses competed for one bucket of feed. Although there was no correlation between rank in the hierarchy and maze learning ability, there was a correlation between body weight and rank in the hierarchy (r = .7, P less than .05). This may indicate either that heavier horses are likely to be dominant or that horses high in dominance gain more weight. Maternal deprivation did not appear to seriously retard learning of a simple maze by foals, although the orphans moved more slowly initially. The lack of maternal influence on learning is also reflected in the lack of correlation between the mare's learning ability and that of her foal. Young horses appear to learn more rapidly than older horses.

Age Factors↗
PubMed2004

Learning and strain among newcomers: a three-wave study on the effects of job demands and job control.

The present 3-wave longitudinal study was an examination of job-related learning and strain as a function of job demand and job control. The participants were 311 newcomers to their jobs. On the basis of R. A. Karasek and T. Theorell's (1990) demand-control model, the authors predicted that high demand and high job control would lead to high levels of learning; low demand and low job control should lead to low levels of learning; high demand and low job control should lead to high levels of strain; and low demand and high job control should lead to low levels of strain. The relation between strain and learning was also examined. The authors tested the hypotheses using ANCOVA and structural equation modeling. The results revealed that high levels of strain have an adverse effect on learning; the reverse effect was not confirmed. It appears that Karasek and Theorell's model is very relevant when examining work socialization processes.

Adult↗
PubMed1998

Ex vivo nerve growth factor gene transfer to the basal forebrain in presymptomatic middle-aged rats prevents the development of cholinergic neuron atrophy and cognitive impairment during aging.

Nerve growth factor (NGF) is able to restore spatial learning and reverse forebrain cholinergic neuron atrophy when administered intracerebrally to behaviorally impaired aged rats. In the present study, behaviorally unimpaired, middle-aged rats (14-16 months old) received transplants of ex vivo transduced, clonal NGF-secreting immortalized neural progenitor cells, bilaterally in the nucleus basalis and septum. During the subsequent 9 months the aged control animals developed the expected impairment in spatial learning in the water maze task, whereas the animals with NGF-secreting grafts maintained a performance level not different from the 12-month-old control rats. The marked age-induced atrophy (-25%) of the cholinergic neurons in medial septum and nucleus basalis, seen in the aged control rats, was not present in the NGF-treated aged animals. 3H-labeled thymidine autoradiography showed that the transduced cells survived well and had become integrated into the host tissue surrounding the injection sites, and reverse transcription-PCR analysis revealed expression of the NGF transgene, at both 4 and 9 months postgrafting, in the grafted tissue. The results show that long-term supply of NGF from ex vivo transduced immortalized neural progenitor cells locally within the nucleus basalis and septum can prevent the subsequent development of age-dependent neuronal atrophy and behavioral impairments when the animals reach advanced age.

Aging↗
PubMed1975

Delayed alternation learning under electrical (blocking) stimulation of the caudate nucleus in the cat.

Of 9 cats with electrodes implanted in the dorsolateral caudate nucleus, 4 had previously reached criterion on a delayed alternation task. Tested under alternating conditions of stimulation and nonstimulation, these 4 animals showed a significant performance decline with stimulation. When a marker was placed on one response panel, performance under stimulation did not decline. Stimulation did not affect the learning of a visual discrimination. The remaining 5 cats were trained on delayed alternation with alternating stimulation and nonstimulation conditions. Under stimulation, performance remained near chance levels. These animals were tested on position learning and reversal, and under unilateral stimulation. The results support the view that the caudate nucleus and prefrontal cortex mediate separate aspects of delayed response behavior.

Animals↗
PubMed1994

Effect of nutritional and environmental restrictions on discrimination learning behaviour of juvenile rats.

Effects of nutritional and environmental restrictions on discrimination learning in a single unit black/white T-maze were studied in albino rats. Nutritional restrictions were imposed by 25 and 50% dietary restriction and environmental restrictions were given for 3 and 6 weeks. Both the restrictions were imposed at 46th day after birth. Long-term (6 weeks) environmental restriction significantly impaired the original and reversal discrimination learning, however, short-term (3 weeks) restriction had no effect. Nutritional (dietary) restrictions, on the other hand, had no effect on both learning performances. Interaction between these two variables was also statistically insignificant.

Animals↗
PubMed2006

fMRI investigation of cortical and subcortical networks in the learning of abstract and effector-specific representations of motor sequences.

A visuo-motor sequence can be learned as a series of visuo-spatial cues or as a sequence of effector movements. Earlier imaging studies have revealed that a network of brain areas is activated in the course of motor sequence learning. However, these studies do not address the question of the type of representation being established at various stages of visuo-motor sequence learning. In an earlier behavioral study, we demonstrated that acquisition of visuo-spatial sequence representation enables rapid learning in the early stage and progressive establishment of somato-motor representation helps speedier execution by the late stage. We conducted functional magnetic resonance imaging (fMRI) experiments wherein subjects learned and practiced the same sequence alternately in normal and rotated settings. In one rotated setting (visual), subjects learned a new motor sequence in response to an identical sequence of visual cues as in normal. In another rotated setting (motor), the display sequence was altered as compared to normal, but the same sequence of effector movements was used to perform the sequence. Comparison of different rotated settings revealed analogous transitions both in the cortical and subcortical sites during visuo-motor sequence learning-a transition of activity from parietal to parietal-premotor and then to premotor cortex and a concomitant shift was observed from anterior putamen to a combined activity in both anterior and posterior putamen and finally to posterior putamen. These results suggest a putative role for engagement of different cortical and subcortical networks at various stages of learning in supporting distinct sequence representations.

Adult↗
PubMed1984

Differential effects of prefrontal lesions and combined prefrontal and limbic lesions on subsequent learning performance in the cat.

On the basis of a previous experiment (Irle & Markowitsch, 1983) in which triple limbic lesions as opposed to double limbic lesions in the cat failed to impair the learning behavior of these animals, the effects of a lesion in a fourth brain structure, in addition to the original ones, were examined. Two groups of cats were given lesions in either the prefrontal cortex alone or in the prefrontal cortex, the anterior thalamus, the mamillary bodies, and the subiculum and subsequently tested in the acquisition of a visual reversal, a delayed alternation, and an active two-way avoidance task. Compared with control cats, cats with prefrontal lesions were strongly impaired in the acquisition of the visual reversal task and the delayed alternation task but only slightly impaired in the acquisition of the active two-way avoidance task. In contrast, animals with combined prefrontal cortical, anterior thalamic, mamillary, and subicular lesions were unimpaired in the acquisition of the visual reversal task, slightly facilitated in the acquisition of the active two-way avoidance task, but impaired in the acquisition of the delayed alternation task similarly to the animals with prefrontal lesions. The superior performance rates of the animals with fourfold lesions are considered to be due to a lesion-induced functional shift acting on intact brain structures which, prior to massive limbic lesions, remain inhibited or otherwise suppressed. The failure of the animals with fourfold lesions in the delayed alternation task indicates that the functions underlying this type of behavior cannot be compensated for or, alternatively, that a prefrontal lesion is not sufficient to disinhibit other structures involved in the same behavior.

Animals↗
PubMed2003

Attenuation of sucrose reinforcement in dopamine D1 receptor deficient mice.

Dopaminergic systems are thought to mediate the rewarding and reinforcing effects of palatable food. However, the relative contribution of different dopamine receptor subtypes is not clear. We used dopamine D1 receptor deficient mice (D1 -/-) and their wild-type and heterozygous littermates to study the role of the D1 receptor in palatable food reinforced behaviour using operant responding and free access paradigms. Non-deprived mice were trained to press a lever for sucrose pellets under three schedules of reinforcement including fixed ratios (FR-1 and FR-4) and a progressive ratio (PR). Responding on one lever was reinforced by the delivery of a sucrose pellet or solution while responding on a second lever had no programmed consequences. Initially, D1 mutant mice took longer to learn to discriminate between the two levers and had significantly lower operant responding for sucrose pellets and solution than wild-type and heterozygous mice under all schedules of reinforcement. Food deprivation enhanced responding on the active lever in all mice although it remained significantly lower in D1 -/- mice than in control mice. Following extinction of sucrose reinforcement and reversal of the levers, D1 -/- mice showed deficits in extinguishing and reversing previously learned responses. Home cage intake and preference of sucrose pellets and solutions when given under free-choice access paradigms were similar among the groups. These results suggest that the dopamine D1 receptor plays a role in the motivation to work for reward (palatable food) but not in reward perception and is critical in learning new but relevant information and discontinuing previously learned responses.

Analysis of Variance↗
PubMed2003

Inhibitory control following perinatal brain injury.

Evidence from developmental, lesion, and neuroimaging studies indicates that the prefrontal cortex plays a major role in executive abilities, including inhibitory control. Proficient executive performance, however, relies not only on the integrity of the prefrontal cortex but also on its interactions with other brain regions. In the current study, the authors focused on the effect that early damage to the white matter tracts interconnecting prefrontal and other brain regions has on inhibitory control. Data were collected from 13 children with bilateral spastic cerebral palsy and from a control group of 20 children with no history of neurologic compromise. Converging evidence from 3 separate paradigms is presented that strongly suggests these children experience impairments in inhibitory control. Findings are discussed within the context of current cognitive and neuroanatomical models of inhibition.

Adolescent↗
PubMed2006

Intrathecal infusions of anisomycin impact the learning deficit but not the learning effect observed in spinal rats that have received instrumental training.

Previous research has shown that spinally transected rats will learn to maintain a flexion response when administered shock contingent upon leg position. In short, a contingency is arranged between shock delivery and leg extension so that Master rats exhibit an increase in flexion duration that lasts throughout the training session. Furthermore, when Master rats are later tested they reacquire the flexion response in fewer trials, indicative of some savings. As a control, a second group of spinal rats (Yoked rats) are given shock irrespective of leg position (noncontingent shock). These animals fail to show the same increase in leg flexion duration. Interestingly, when Yoked rats are later tested with a shock contingency in place, they still fail to learn (learning deficit). The present experiments were designed to determine whether both forms of instrumental learning in spinal animals require de novo protein synthesis. As such, we administered various doses of anisomycin intrathecally prior to training. Additionally, spinal rats were trained and tested either immediately or 24 h after test. We found that only the highest dose of anisomycin (125 microg/microl) had an effect in Yoked animals that were tested 24 h after training. Specifically, the highest dose of anisomycin reversed the learning deficit in those animals. Moreover, anisomycin had a similar effect when administered prior to training and immediately following training, but not 6 h after training. Finally, the results demonstrated that the observed effect of anisomycin was not due to state-dependency.

Animals↗