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PubMed1982

Analysis of behavioural responses to an ACTH analog in CXB/By recombinant inbred mice.

Male mice of the C57BL/6By and BALB/cBy inbred strains, their reciprocal F1 hybrids, and 7 recombinant inbred strains, were tested for open-field activity, a shock-motivated successive reversal position discrimination problem in a T-maze, and a toggle box exploration task. The test battery was repeated one month later. Finally, mice were tested for the acquisition and extinction of a taste aversion conditioned by ethanol injection. Mice of each strain were tested after injection with saline or one of 3 doses of an ACTH analogue. Highly significant genotypic differences were found for all measures, an expected result. The strain distribution pattern seen in the toggle box suggested single gene mediation of exploratory activity after habituation. One aspect of avoidance responding and extinction of conditioned taste aversion also yielded strain distribution pattern consistent with single gene control. Peptide treatment reduced internal field crossings in the open field. This effect was not strain dependent. Peptide treatment had no effect on T-maze learning, conditioned taste aversion, or toggle-box exploration.

Adrenocorticotropic Hormone↗
PubMed2004

Fear conditioning is associated with altered integration of PLC and ERK signaling in the hippocampus.

The extracellular signal-regulated protein kinases (ERKs) are proline-directed, serine/threonine kinases that regulate a variety of cellular functions, including proliferation, differentiation, and plasticity. In the present report, we provide evidence that ERK2 and phosphatidylinositol-specific phospholipase C (PLC)-beta and -gamma isozymes interact in the rat hippocampal formation. We found that anti-PLC-beta1a, -beta2, -beta4, -gamma1 and -gamma2, but not -beta3, immune complexes isolated from rat hippocampal formation postnuclear fractions contain anti-ERK2 immunoreactivity. Further, we show that PLC catalytic activity is associated with anti-ERK2 immunoprecipitates isolated from the hippocampal formation, and that the amount of enzyme activity is significantly increased following fear-conditioned learning. The observed interactions may be mediated by consensus sequences conforming to an ERK2 docking site, termed a D-domain, that we identified in PLC-beta1a, -beta2, -beta4 -gamma1 and -gamma2. Based on these results, we propose that PLC-beta and PLC-gamma isozymes form signaling complexes with ERK2 in rat brain, and these complexes play critical roles in learning and memory, as well as a variety of other neuronal functions.

Animals↗
PubMed1992

Designing studies of drug conditioning in humans.

There has been much recent interest in the possibility that signals for drug use in humans acquire the ability to evoke classically conditioned (learned) states which motivate drug taking. Much data now suggest that cues paired with drug use come to elicit physiological responses and subjective reports of drug-related feelings like craving and withdrawal. However, the designs employed do not permit the conclusion that the observed responding results from classical conditioning. Studies which look directly at conditioning in the laboratory by pairing neutral stimuli with drug administration have not provided appropriate controls for unlearned effects such as sensitization or pseudo-conditioning. Similarly, studies which assess responding to cues thought to signal drug use in the natural environment (e.g., the sight of someone injecting heroin) have not adequately assessed whether such cues have unconditioned (unlearned) effects. Determining whether responding to drug-related cues results from classical conditioning has important implications for the development of drug treatments. Consequently, the purpose of the present review is to outline a set of criteria for determining that responses to drug-related stimuli in humans are learned. Existing studies are reviewed in light of these criteria and paradigms for further work are suggested.

Conditioning, Classical↗
PubMed1989

Unilateral periarcuate and posterior parietal lesions impair conditional position discrimination learning in the monkey.

Monkeys were trained on a conditional position discrimination in which the conditional cue was a light blinking at two distinct rates and the discriminanda (illuminated buttons) appeared in varying symmetrical positions of eccentricity. Unilateral arcuate, posterior parietal, or principal sulcus lesions were performed at criterion. The monkeys were tested to recovery when a homologous lesion was made contralaterally. The first of two analyses examined a period of 4 weeks following each lesion; the unit of analysis was lesions. The arcuate and parietal lesions produced impairments on both widely eccentric and central discriminanda locations; initially, virtually all responses were deflected to the ipsilateral side. There was significant improvement after the arcuate and parietal lesions from weeks 1 to 4. An analysis of total trials to criterion showed major deficits from the second arcuate and parietal lesions, with the arcuate lesion impairment being particularly severe. These results establish that a spatial concept of left vs right is seriously deranged by unilateral lesions of cortical association areas involved in spatial orientation and discrimination.

Animals↗
PubMed1991

A developmental comparison of the effectiveness of encoding tasks.

In Experiment 1, the free-recall performance of young children, college students, and older adults was examined. Subjects encoded words by simply learning them, by studying them in either base or elaborate sentence frames, or by constructing sentences. Overall recall was better for the college students than for the children or for the older adults, and the college students recalled best in the simple learning condition. The young children recalled best in the sentence construction condition; recall by older adults did not vary as a function of the encoding tasks. In Experiment 2, college students and older adults recalled a categorized list, encoding the words by simply learning them, by studying them in elaborate sentence frames, or by completing word fragments. For both age groups, simple learning produced the highest level of recall. These results suggest that organization provides the most effective encoding system and that older adults may need a more obvious basis for organization than do younger adults. Younger and older adults recalled equally well only when organization was discouraged by conceptual processing.

Adult↗
PubMedDate not supplied

[Food getting conditioned reflexes in hedgehogs].

The object of the study were the characteristics of formation of complex food-procuring conditioned reflexes in hedgehogs to visual stimuli of different complexity, to a simultaneous complex, and the interaction of visual and auditory sensory modalities. It has been shown that hedgehogs are capable of learning to choose one of the three simultaneously presented visual stimuli and perform a sequence of complex motor behavioral acts in stage-by-stage learning. Conditioned reflexes to stimuli of different modality were elaborated with difficulty only at their interaction. Higher nervous activity of hedgehogs (insectivorous) is characterized by primitive organization, weakness of inertness of nervous processes and limited integrative possibilities.

Animals↗
PubMed2003

An FMRI study of the role of the medial temporal lobe in implicit and explicit sequence learning.

fMRI was used to investigate the neural substrates supporting implicit and explicit sequence learning, focusing especially upon the role of the medial temporal lobe. Participants performed a serial reaction time task (SRTT). For implicit learning, they were naive about a repeating pattern, whereas for explicit learning, participants memorized another repeating sequence. fMRI analyses comparing repeating versus random sequence blocks demonstrated activation of frontal, parietal, cingulate, and striatal regions implicated in previous SRTT studies. Importantly, mediotemporal lobe regions were active in both explicit and implicit SRTT learning. Moreover, the results provide evidence of a role for the hippocampus and related cortices in the formation of higher order associations under both implicit and explicit learning conditions, regardless of conscious awareness of sequence knowledge.

Hippocampus↗
PubMed1965

INTEROCULAR TRANSFER OF DISCRIMINATIONS IN THE PIGEON.

Pigeons with one eye covered were trained to discriminate intensities or colors of stimuli located to one side of the head, or intensities, colors or forms of stimuli located in front of the beak. Each discrimination transferred to the covered eye, even when previous training with the covered eye included the reversal of the tested discrimination. Pigeons also were able to learn conditional discriminations in which appropriate responding depended on which eye was covered.

Animals↗
PubMed2003

Enactment effect in memory: evidence concerning the function of the supramarginal gyrus.

Experimental behavioral data show that written action descriptions are remembered better when encoded by enacting them compared with merely verbal encoding. To explore this facilitating effect of encoding by performing actions ('enactment effect'), a functional magnetic resonance imaging (fMRI) study was conducted with n=18 normal subjects. During a learning condition, subjects encoded action phrases like 'cut the bread' either by reading aloud or by enacting them. The same phrases plus additional distractors were presented during fMRI scanning, and the task was to decide (yes/no key press) whether a displayed phrase was previously learned or whether it was a new one. Retrieval--independent of encoding type--activated anterior cingulate, SMA, and visual cortex bilaterally. Activations of the inferior frontal and sensorimotor cortex, and the precentral sulcus, were only left sided. The right cerebellum was also activated. The subtraction of the brain activations in the verbal condition from the enactment condition resulted in significant clusters located in middle temporal and inferior parietal left cortical areas, and, on the right side, in superior temporal, postcentral and inferior parietal cortical areas. Most striking were the bilateral inferior parietal activations, covering the supramarginal gyrus (SMG). Therefore it is concluded that SMG may be a central structure in a neurofunctional explanation of the enactment effect.

Adult↗
PubMed1992

Antagonism of drug discrimination learning within the conditioned taste aversion procedure.

Animals injected with morphine prior to the presentation of a saccharin-LiCl pairing and the morphine vehicle prior to saccharin alone rapidly acquired the drug discrimination, avoiding saccharin following the administration of morphine and consuming saccharin following its vehicle after only four conditioning trials. Once stimulus control was established, the opiate antagonist naloxone (1 mg/kg) was administered prior to morphine in a test of its ability to antagonize the morphine stimulus. Pretreatment times ranged from 10 to 180 min. Naloxone antagonized the stimulus properties of morphine for all subjects, although there were individual differences in the onset, duration (time course) and degree of antagonism. Together with the rapid acquisition typically reported in this design, the fact that antagonism was demonstrated in the present study suggests that the conditioned taste aversion procedure may be useful in the general assessment of drug discriminations.

Animals↗
PubMed2003

A mouse model of prenatal ethanol exposure using a voluntary drinking paradigm.

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.

Alcohol Drinking↗
PubMed2003

Chronic prenatal ethanol exposure impairs conditioned responding and enhances GABA release in the hippocampus of the adult guinea pig.

In this study, we assessed the effects of chronic prenatal ethanol exposure (CPEE) on spatial navigation in the water maze, conditioned responding using food-reinforced lever pressing, and amino acid neurotransmitter release from the hippocampus of the adult guinea pig. Pregnant guinea pigs were treated with ethanol (3 g/kg of maternal body weight/day), isocaloric-sucrose/pair-feeding, or water throughout gestation. Adult offspring were trained in two-lever operant chambers to respond for sucrose pellets, with one lever designated as the reward lever. There were no group differences in response acquisition or lever discrimination on a fixed-ratio 1 (FR-1) schedule. During extinction sessions, CPEE offspring maintained higher levels of responding on the previously reinforced lever, suggesting that CPEE increases perseveration and/or impairs response inhibition but does not affect operant responding for an appetitive reinforcer or the ability to discriminate rewarding from nonrewarding stimuli. In contrast, there was no effect of CPEE on performance in the water maze in the maternal ethanol regimen used in this study. CPEE did not alter electrically evoked glutamate or GABA release from hippocampal brain slices. However, when slices were tested after delivery of a tetanizing stimulation (five 5-s trains at 100 Hz), post-tetanic potentiation of electrically stimulated GABA release was greater in hippocampal slices obtained from CPEE offspring, whereas post-tetanic potentiation of electrically stimulated glutamate release was unaffected. These data suggest that conditioned learning is a sensitive behavioral measure of CPEE-induced brain injury. Increased activity-dependent potentiation of GABA release in the hippocampus may contribute to alterations in synaptic plasticity observed in CPEE offspring.

Animals↗
PubMedDate not supplied

Effects of perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on spatial and visual reversal learning in rats.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that has been shown to alter spatial and visual learning following developmental exposure. The current study examined the effects of gestational and lactational exposure to TCDD on spatial and visual discrimination/reversal learning (spatial and visual RL) in rats using two-lever operant testing chambers. Pregnant Sprague-Dawley rats (10 per dose) received either 0 or 0.1 microg/kg TCDD per orem in corn oil from gestational day (GD) 10 to GD 16. One male and one female from each litter were tested beginning at 100 days of age. For spatial RL, animals were reinforced for pressing the lever associated with the correct spatial location (either left or right). For visual RL, the animals were reinforced for pressing the lever associated with the correct visual stimulus (either the illuminated or nonilluminated cuelight). After reaching 85% correct for two consecutive days, the opposite spatial location or visual cue was reinforced. Five reversals were conducted for spatial RL, and two reversals for visual RL. For spatial RL, there were no differences between the TCDD-exposed and control rats in total number of errors committed. However, an in-depth analysis of errors in four different phases of the learning process revealed that TCDD-exposed rats made more errors early in learning when they were just beginning to learn the new reinforcement contingencies. The importance of this increase in errors during the initial stage of learning is unclear, given that there was no increase in overall errors to criterion. For visual RL, there was a reduction in errors on original learning (OL) for TCDD-exposed males, while TCDD-exposed females exhibited a reduction in errors on the second reversal. Subsequent response pattern analyses revealed that the facilitation in performance was due to a more rapid transition through the early phase of learning. Why males were improved on OL and females were not until the second reversal is unknown, but the different patterns could reflect differences in learning style in male and female rats. In keeping with previous research, the results of the current study underscore the fact that (1) alterations in cognitive function observed following early TCDD exposure are very subtle and (2) under some conditions, learning is actually facilitated, rather than impaired, in TCDD-exposed animals.

Analysis of Variance↗
PubMed1989

Age deficits in recall under optimal study conditions.

Young and older adults studied lists of words under both standard and optimal study conditions for subsequent free recall. Under optimal conditions, the participants studied each word for as long as they wished, were allowed to take notes, and were encouraged to actively use whatever strategies they thought would maximize recall. Both age groups recalled more words under optimal study conditions than under standard conditions, but the improvement was greater for the young adults. This increase in the age-related recall deficit was not due to differences in study time. The results suggest that standard laboratory memory tasks do not overestimate the memory deficits of older adults because of a failure to provide either optimal learning conditions or sufficient study time.

Adolescent↗
PubMed1995

The effects of visual and auditory models on the learning of a rhythmical synchronization dance skill.

The purpose of this study was to investigate the effect of visual and auditory concurrent models on the acquisition of a rhythmical synchronization task. Subjects attempted to synchronize a series of dance steps to the beat of two auditory rhythms. Subjects performed five trial blocks in one of four practice conditions: (a) audio-visual (auditory rhythms combined with a visual model), (b) audio-auditory (auditory rhythms combined with an auditory model), (c) auditory only (auditory rhythms with no model), and (d) visual only (no auditory rhythms but exposure to a visual model). Rhythmical timing and synchronization accuracy served as the dependent variables. Results revealed no practice condition learning differences for rhythmical timing. For synchronization accuracy, the audio-auditory group produced significantly lower error scores at acquisition, but no differences were found at retention. Apparently, the availability of models created an information dependency that resulted in a decrease of performance and, consequently, no group differences in retention.

Adolescent↗
PubMed1989

Stimulus class formation and stimulus-reinforcer relations.

This study examined stimulus class membership established via stimulus-reinforcer relations. Mentally retarded subjects learned conditional discriminations with four two-member sets of visual stimuli (A, B, C, and D). On arbitrary-matching trials, they selected comparison stimuli B1 and B2 conditionally upon samples A1 and A2, respectively, and C1 and C2 conditionally upon B1 and B2, respectively. On identity-matching trials, they selected all stimuli as comparisons conditionally upon identical stimuli as samples. Throughout training, correct selections of A1, B1, C1, and D1 were followed by one reinforcer, R1, and those of A2, B2, C2, and D2 were followed by another, R2. Subsequent tests documented the formation of two four-member stimulus classes, A1-B1-C1-D1 and A2-B2-C2-D2. The class membership of the A, B, and C stimuli could have been based on equivalence relations that resulted from the arbitrary-matching training. D1 and D2 had never appeared on arbitrary-matching trials, however. Their class membership must have been based on relations with R1 and R2, respectively. Results thus confirm a previous finding that stimulus classes can be expanded via stimulus-reinforcer relations. They also define more precisely the potential nature of those classes and the conditions under which class membership can be established.

Adolescent↗
PubMed1992

Synaptic reorganization in developing and adult nervous systems.

Evidence is accumulating that synapse reorganization already starts during development, soon after first synapses appear. Although remodeling continues throughout ontogenesis, there are apparently (critical) periods which are characterized by enhanced synaptic reorganization. In certain parts of the peripheral and central nervous system, synapses may undergo remodeling which leads to changes in their transmission efficiency or complete elimination of the synaptic junctions, even in adulthood. Synaptic reorganization includes progressive and regressive changes on branches of dendritic and/or axonal processes that accompany the formation and elimination of synapses. Three modes of elimination are presently known: Physiological cell death of synaptically connected neurons is involved, especially during certain developmental periods, during hormonally induced metamorphosis and in the olfactory bulb. Synaptic disconnection ("stripping") and lysosomal degradation predominantly of presynaptic elements occur under different conditions. In order to undergo plastic changes, neurons seem to respond to exogenous or intrinsic factors such as lesions (partial deafferentation and axotomy), long-lasting changes in neuronal activity (e.g. drug application and sensory deprivation), hormonal influences (e.g. sexual hormones) or learning conditions.

Aging↗