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At least 379 records · Page 21Linked to original sources
PubMed2006

Postnatal exposure to diisopropylfluorophosphate enhances discrimination learning in adult mice.

Visual discrimination and reversal learning were tested in adult C57Bl/6 mice that had been treated on postnatal days (PND) 4-10 with diisopropylfluorophosphate (DFP), an acetylcholinesterase inhibitor. DFP-treated mice attained the learning criterion in the Y maze significantly earlier than saline-treated mice. Female mice treated with DFP showed a more rapid decline in errors in the initial discrimination task, compared to female mice treated with saline. There was no effect of DFP treatment on learning the reverse discrimination. The data suggest that long-lasting effects of treatment with an acetylcholinesterase inhibitor can improve discrimination learning, similarly to the improvement reported by acute administration in adults.

Animals↗
PubMed2004

Different underlying impairments in decision-making following ventromedial and dorsolateral frontal lobe damage in humans.

Ventromedial prefrontal cortex (VMF) damage can lead to impaired decision-making. This has been studied most intensively with the Iowa gambling task (IGT), a card game that asks subjects to overcome an initial attraction to high-payoff decks as losses begin to accrue. VMF subjects choose from the high risk decks more often than controls, but the fundamental impairments driving poor performance on this complex task have yet to be established. There is also conflicting evidence regarding the role of the dorsolateral prefrontal cortex (DLF) in this task. The present study examined whether poor performance on the IGT was specific for VMF damage and whether fundamental impairments in reversal learning contributed to IGT performance. We found that both VMF and DLF damage leads to impaired IGT performance. The impairment of VMF subjects, but not of DLF subjects, seems to be largely explained by an underlying reversal learning deficit.

Decision Making↗
PubMed1982

Hyperstriatal lesions in pigeons (Columba livia): effects on retention and perseveration.

Two experiments explored the possibility that lesions of avian hyperstriatum, which disrupt reversal learning, might have that effect through a potentiation of the influence of proactive interference. Neither experiment found any evidence to suggest excessive interference in hyperstriatal pigeons, from preceding training on a position (or color) discrimination, on retention of a color (or position) discrimination, and this was true both after a short (30 min) and after a long (6 or 7 day) retention interval. There was, however, evidence of a disturbance, not easily interpreted, in retention following the lesions. There was also convincing evidence, from both experiments, for the disruption by hyperstriatal lesions not only of reversal learning but also of tasks not involving reversals, a disruption that suggests a general tendency to perseverate in hyperstriatal birds.

Animals↗
PubMed1990

Behavioral and neurochemical changes associated with chronic exposure to low-level concentration of pesticide mixtures.

In order to assess behavioral and neurochemical changes resulting from pesticide exposure, food-restricted male weanling rats were exposed for 90 d to low doses (1 ppb-10,000 ppb range) of individual pesticides (aldicarb, metribuzin, or methomyl) or mixtures of them. During exposure, rats were trained to run a T-maze and tested for spatial discrimination reversal learning. At sacrifice, three brain regions (cortex, hippocampus, and neostriatum) were assayed for the neurotransmitters dopamine, acetylcholine, and serotonin. Animals treated with a mixture of two insecticides and one herbicide were found to have slower speeds in maze-running (motor control) and also had altered levels of choline in their neostriatums. Rats treated with one herbicide compound (metribuzin) took longer to learn on two reversals; this group also had a significantly lower acetylcholine/choline ratio in their hippocampus.

Aldicarb↗
PubMed1990

[Right/left discrimination learning in rat pups neonatally treated with 6-hydroxydopamine].

At 2 and 4 days of age, rat pups were treated with 6-hydroxydopamine (6-OHDA; 70 micrograms, ivt) following desmethylimipramine (20 mg/kg, sc) pretreatment. Spontaneous activity test in a novel cage at 16 and 17 days of age revealed a sustained higher level of locomotor activity in 6-OHDA-treated rats, which was characterized by a deficit of habituation. For right/left discrimination learning trained from 18 days of age, "homing" was used as an reinforcer, i.e., pups could enter the goal area adjacent to home cage if they chose a predetermined correct arm of T-maze. Rats were trained 10 trials a day until they attained the learning criterion (at least 17 correct choices in 2 days). Thereafter, they were re-trained for the reversal learning to the criterion (at least 8 correct choices in a day). 6-OHDA-treated rats were required significantly more trials to attain the learning criterion both in the original and the reversal learnings. Biochemical assay confirmed a marked depletion of brain dopamine contents in striatum, cortex and midbrain with thalamus in 6-OHDA-treated rats. Therefore, the neonatal depletion of brain dopamine produced hyperactivity (habituation deficit) and a discrimination deficit during the developmental period.

Animals↗
PubMed2001

Emotion-related learning in individuals prenatally exposed to alcohol: an investigation of the relation between set shifting, extinction of responses, and behavior.

The association between deficits in emotion-related learning, conceptual set shifting, and behavioral problems was investigated in individuals with substantial prenatal alcohol exposure. Twenty subjects with confirmed prenatal alcohol exposure (10 of whom were diagnosed as having Fetal Alcohol Syndrome) and 20 normal controls matched for age, gender, and ethnic background participated. The two groups were administered a battery of tests including two tests of emotion-related learning (visual discrimination reversal and extinction of reward-response associations), tests of conceptual set shifting and intellectual ability, and behavioral measures. The alcohol-exposed group made fewer reversals than the control group in visual discrimination reversal and exhibited more variability in extinction. These group differences remained significant after controlling for intellectual ability and conceptual set shifting. Variability in extinction and two measures of set shifting, perseverative errors on the Wisconsin Card Sorting Test and omission errors on reversal learning, were found to be robust predictors of parent-rated behavioral problems.

Adolescent↗
PubMed1998

Behavioural, neurochemical and neuroanatomical effects of chronic postnatal N-nitro-L-arginine methyl ester treatment in neonatal and adult rats.

In the present study we evaluated the consequences of interference with nitric oxide synthesis during development on brain function and behaviour in later life. Rat pups received a daily injection of the nitric oxide synthase inhibitor N-nitro-L-arginine methyl ester (L-NAME, 25 mg/kg, s.c.) from postnatal day 0 to 24. At postnatal day 8 L-NAME-treated rats had enlarged and heavier stomachs, while body weights appeared to be reduced. The stomachs were not affected in size and weight anymore at postnatal day 24, whereas the body weights were still reduced by the L-NAME treatment, although they soon recovered after termination of the treatment. At four months-of-age, rats were tested in non-cognitive (open field) and cognitive (Morris water escape, two-way active avoidance) tasks. Open field behaviour of adult rats postnatally treated with L-NAME was not affected. In the water escape task there were no differences between the saline and L-NAME-treated rats in spatial discrimination learning and spatial reversal learning. Furthermore, postnatal L-NAME treatment did not have an effect on the acquisition of the two-way active avoidance task. Subsequently, we tested rat pups during the L-NAME treatment at postnatal day 19 through 24 in the open field and the two-way active avoidance task. L-NAME treatment appeared to increase the behavioural activity in the open field. There was no difference in behaviour in the active avoidance task between saline and L-NAME-treated rats. Biochemical and immunocytochemical studies showed that at postnatal day 8 the basal cyclic GMP level was reduced, while the cyclic GMP formation due to incubation with the nitric oxide donor sodium nitroprusside appeared to be increased in the hippocampus, striatum and frontal cortex of L-NAME-treated rats. Hence, nitric oxide synthase was inhibited whereas the soluble guanylyl cyclase activity may be increased in sensitivity. At postnatal day 24 basal cyclic GMP levels and nitric oxide-mediated cyclic GMP formation in the brain structures of L-NAME-treated rats had normal values again. Taken together, the findings of this study suggest that postnatal inhibition of nitric oxide synthase has profound neurochemical effects during development and may have short-lasting effects on non-cognitive behaviour, but it does not affect behaviour and brain function in later life.

Animals↗
PubMed1996

Autism, Asperger's syndrome and the Crick-Mitchison theory of the biological function of REM sleep.

Autism, Asperger's syndrome and other autistic syndromes are developmental brain disorders that cause serious impairments in communication, social interaction, empathy, mood and play. In addition to such deficits, the autistic syndromes involve pathologically high levels of repetitive, stereotypic, ritualistic, compulsive or obsessive behavior, together with extreme resistance to change. According to the Crick-Mitchison theory of the biological function of rapid eye movement sleep, normal brain development in the fetus and infant depends on undisrupted function of a 'reverse learning' mechanism during rapid eye movement sleep. Could abnormalities in this hypothetical reverse learning during rapid eye movement sleep in the fetus explain some aspects of the autistic syndromes? Does the Crick-Mitchison theory suggest if a drug could interfere with rapid eye movement sleep and cross the placental barrier, then that drug might cause developmental brain disorders in the fetus? Should all pregnant women completely avoid caffeine or any agent that might disrupt serotonergic or cholinergic systems?

Autistic Disorder↗
PubMed1994

Increase of synaptic density and memory retention by a peptide representing the trophic domain of the amyloid beta/A4 protein precursor.

The secreted form (sAPP) of the Alzheimer amyloid beta/A4 protein precursor (APP) has been shown to be involved in the in vitro regulation of fibroblast growth and neurite extension from neuronal cells. The active site of sAPP responsible for these functions is within a small domain just C-terminal to the Kunitz-type protease inhibitor (KPI) insertion site. We report here that a 17-mer peptide, containing this active domain of sAPP, can induce cellular and behavioral changes when infused into rat brains. After 2 weeks of APP 17-mer peptide infusion, the animals were tested for reversal learning and memory retention and were sacrificed for morphological examination of brains. We found that administration of the APP 17-mer peptide resulted in an 18% increase in the number of presynaptic terminals in the frontoparietal cortex. At the behavioral level, 17-mer-infused animals with nonimpaired learning capability showed an increased memory retention that seemed to interfere with reversal learning performance. This APP 17-mer effect on memory retention was not observed in animals with impaired initial learning capacity. These results suggest that APP is involved in memory retention through its effect on synaptic structure.

Amino Acid Sequence↗
PubMed1996

Colour learning in the hawkmoth Macroglossum stellatarum

Newly eclosed specimens of the day-active hawkmoth Macroglossum stellatarum were trained to artificial flowers in dual-colour choice situations. Learning curves were obtained from learning and reversed-learning experiments. Initially, learning behaviour was influenced by innate colour preferences. In comparison with other lepidopterans, Macroglossum stellatarum learns well. When trained in a dual-choice situation, the moths learned not only to visit the rewarded colour but also to avoid the unrewarded colour. These good learning abilities are discussed in the context of the biology of the species.

Journal Article↗
PubMed2005

An investigation of the relationship between response latency across several cognitive tasks in the beagle dog.

Response latencies (RLs) extracted from simple motor tasks are a commonly used index of human intelligence. To date few human or animal studies have investigated the relationship between an individuals RL scores across a number of diverse cognitive tasks: Does RL remain consistent between individuals across several cognitive domains? Thus, the current study examined how RL measures gathered from beagle dogs (n=13) tested on three different cognitive tasks were related. RL scores were collected following both discrimination and reversal learning and a test of visuospatial memory, the 3 component delayed non-matching to position (3-DNMP) task. RL scores were recorded from the time the choice stimulus was presented until the animal selected a response. Results indicated that strong correlations emerged between 3-DNMP RLs and both the discrimination and reversal RLs, indicating that animals that responded fast on the 3-DNMP task also responded fast on the discrimination and reversal tasks. Interestingly, 3-DNMP RLs were more strongly correlated with reversal learning RLs. Finally, when mean RL performance across the three tasks was examined, strong RL differences emerged indicating that animals displayed significantly slower RLs on the 3-DNMP task than on the discrimination task, while reversal RLs remained indistinguishable from both. In conclusion, RLs show high between task correlations, indicating individual differences, and also vary between tasks, probably because of differences in task difficulty. These results further validate the use of RLs as an index of cognition, and also highlight the importance of further studies using animal models.

Animals↗
PubMed1979

Response perseveration in rats exposed to alcohol prenatally.

Pregnant female rats consumed liquid diets containing either 35, 17, or 0% of the total calories as ethanol. Offspring of these females were tested for spontaneous alternation at 21 days of age and for reversal learning in a T-maze shock-escape paradigm at 20--21 days of age. In the spontaneous alternation test, rats exposed to alcohol prenatally took more trials than controls to enter the goal compartment opposite to that initially entered. In the T-maze escape study, alcohol-exposed offspring made more mistakes prior to criteron and more mistakes per trial than controls when the previously incorrect goal was made safe during reversal learning. In both studies linear dose-response functions were found. Furthermore, there was a significant tendency for the within-group variabitliy to increase as the level of prenatal exposure increased, perhaps indicating that the incidence as well as the severity of behavioral dysfunction was dose dependent. The results are interpreted in terms of a delay in the development of a central inhibitory system.

Animals↗
PubMed1995

Effects of mammillary bodies and mediodorsal thalamic lesions on the acquisition and retention of a learning set in mice: paradoxical effect of the intersession interval.

The effects of ibotenic acid lesions of either the mediodorsal thalamus (MD) or the mammillary bodies (MB) on the acquisition and retention of a reversal learning set in a T-maze were studied in mice. Both the MB and MD lesions disrupted performance in this task, but only MD lesions slowed down the rate of learning, MD-lesioned subjects requiring more trials than the other two groups to master the discrimination at the end of the learning phase. Surprisingly, increasing the intersession interval from 24 h to 10 days totally alleviated the deficit of MD-subjects and even improved their performance as compared to the last (8th day) session. The overall results of the study show that both MD and MB lesions do not induce important learning deficits nor anterograde amnesia in the reversal learning set task.

Animals↗
PubMed1995

Legionella pneumophila-induced visual learning impairment reversed by anti-interleukin-1 beta.

Infecting mice with the opportunistic intracellular pathogen Legionella pneumophila markedly inhibited place learning of infected C57BL/6 mice as determined by the Morris water maze test. Mice infected with L. pneumophila evinced much less ability to learn the position of a hidden platform than did normal noninfected mice, which quickly learned the location of the hidden platform and escaped from the cool water of the pool with increasing efficiency. However, infected mice treated with anti-interleukin-1 (anti-IL-1) neutralizing antibody learned the task with about the same efficiency as the controls. When the animals were tested 1 week after learning, control animals remembered the task well and were able to escape with near maximal efficacy. On the other hand, L. pneumophila-infected mice performed as poorly after the 1 week rest as during the training period, indicating that infection blocked learning and not merely performance. Mice infected with L. pneumophila and given the antibody treatment were found to be indistinguishable from controls in that they remembered the task and escaped with good efficiency. Thus, the results of this study suggest that the pro-inflammatory cytokine, IL-1 beta, is involved, at least partly, in the attenuation of spatial navigational learning in mice infected acutely with a sublethal concentration of L. pneumophila. These results, therefore, suggest that cognitive impairment of L. pneumophila-infected mice may be related to the cytokine IL-1 beta and, furthermore, that cytokines may be related to learning and memory changes experienced by individuals suffering acute bacterial infections.

Animals↗
PubMed2006

Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy.

Adult↗
PubMed2006

Learning-induced reversal of the effect of noradrenalin on the postburst AHP.

Pyramidal neurons in the piriform cortex from olfactory-discrimination-trained rats have reduced postburst afterhyperpolarization (AHP), for 3 days after learning, and are thus more excitable during this period. Such AHP reduction is caused by decreased conductance of one or more of the calcium-dependent potassium currents, I(AHP) and sI(AHP), that mediate the medium and slow AHPs. In this study, we examined which potassium current is reduced by learning and how the effect of noradrenalin (NE) on neuronal excitability is modified by such reduction. The small conductance (SK) channels inhibitor, apamin, that selectively blocks I(A)(HP), reduced the AHP in neurons from trained, naïve, and pseudotrained rats to a similar extent, thus maintaining the difference in AHP amplitude between neurons from trained rats and controls. In addition, the protein expression level of the SK1, SK2, and SK3 channels was also similar in all groups. NE, which was shown to enhance I(AHP) while suppressing (S)I(AHP), reduced the AHP in neurons from controls but enhanced the AHP in neurons from trained rats. Our data show that learning-induced enhancement of neuronal excitability is not the result of reduction in the I(AHP) current. Thus it is probably mediated by reduction in conductance of the other calcium-dependent potassium current, sI(AHP). Consequently, the effect of NE on neuronal excitability is reversed. We propose that the change in the effect of NE after learning may act to counterbalance learning-induced hyperexcitability and preserve the piriform cortex ability to subserve olfactory learning.

Animals↗