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Increased extracellular dopamine in the nucleus accumbens of the rat during associative learning of neutral stimuli.

Brain microdialysis was used to study changes in dopamine in the nucleus accumbens and the dorsal striatum during associative learning between two neutral stimuli, flashing light and tone, presented on a paired schedule during stage 1 of a sensory preconditioning paradigm. The tone was subsequently paired with mild footshock using standard aversive conditioning procedures and the formation of a conditioned association between the flashing light and the tone in stage 1 was assessed by measuring the ability of the flashing light to elicit the same conditioned response as the tone when presented at test. The first experiment used behavioural monitoring only, to establish stimulus parameters for subsequent microdialysis experiments. Animals receiving paired presentation of the light and tone in stage 1 showed a conditioned suppression of licking to the light as well as to the tone, indicating that associative learning between the flashing light and the tone had occurred during stage 1, whilst in a separate group of animals given the same stimuli over the same time period but on an explicitly non-paired schedule, the conditioned emotional response was seen to the tone, but not to the light, showing that no association had been formed between the two stimuli during stage 1. In dialysis experiments using the same procedure, we measured a two-fold rise in dopamine in the nucleus accumbens during paired presentation of flashing light and tone, but not during non-paired presentation of the two stimuli. On subsequent test presentation of the two stimuli, we saw increases in accumbal dopamine on presentation of the tone in both groups, reflecting the formation of an association with the footshock in both. However the flashing light elicited an increase in dopamine only in the group which had received paired presentation at stage 1. Thus accumbal dopamine release at test is correlated to the ability of the stimulus to evoke a conditioned response measured behaviourally. Hypotheses of the behavioural function of the mesolimbic dopamine system centre on its role in mediating the effects of biological reinforcers, both rewarding and aversive, conditioned and unconditioned. The present results, showing increases in extracellular dopamine in the nucleus accumbens when an association is formed between two stimuli of which neither is a biological reinforcer nor, prior to formation of the association, affects dopamine levels, suggest a role for accumbal dopamine in the modulation of associative learning in general, not only that involving reinforcement.

3,4-Dihydroxyphenylacetic Acid↗

Analyses of adult age differences in associative learning.

Data from a recent project concerned with adult age differences in associative learning were reanalyzed to identify the processes involved in the age-related differences in trial-by-trial performance in this task. A measure reflecting the failure to retain feedback relevant to one's previous response accounted for a large proportion of the age differences in the early trials of associative learning. The speed with which individuals completed simple processing operations also contributed to the age differences both in measures of accuracy (percentage correct) and in measures of feedback retention.

Adolescent↗

Extinction of associative learning in Hermissenda: behavior and neural correlates.

The nudibranch mollusk Hermissenda crassicornis' normal attraction to light can be suppressed by repeated pairings of light with rotation. The present study examines the effects of extinction procedures on this simple form of associative learning. Presentation of non-reinforced light steps following associative conditioning resulted in an attenuation of phototaxic suppression, evident at both short- and long-term retention intervals. The absence of habituation of phototaxic behavior, coupled with the failure to demonstrate spontaneous recovery of extinguished conditioned suppression, indicates that extinction of associative conditioning in Hermissenda depends little upon non-associative learning processes. Electrophysiological evidence indicates that the Type B photoreceptors, which have been causally implicated in the acquisition and retention of associative learning, play an important role in mediating extinction as well. Enhanced input resistances and light responses of B cells, which are produced by associative training, are absent for animals subsequently exposed to light unaccompanied by rotation. In terms of both behavioral and electrophysiological measures, extinction appears to result primarily from a reversal of the original acquisition process.

Animals↗

Interactions between perinatal and neonatal associative learning defined by contiguous olfactory and tactile stimulation.

Tactile stimulation of the neonate, as performed by the mother during and after delivery, has been described as an effective unconditioned stimulus during early ontogeny (Leon, 1987; Ronca & Alberts, 1994). The present experiments examined the interaction between perinatal and neonatal learning determined by the explicit association between alcohol odor and vigorous body stimulation of the perinatal organism. In Experiment 1, rat fetuses were exposed to either alcohol or saline 10 min prior to cesarean delivery. The alcohol administration procedure here employed was sufficient to provide sensory contamination of the amniotic fluid but avoid fetal alcohol intoxication. Pups in the two prenatal treatments later experienced the smell of alcohol, tactile stimulation, or both stimuli explicitly paired or unpaired. Other postnatal groups were composed of pups that had no explicit experience with either experimental stimulus. Pups subjected to alcohol odor in utero displayed more overall motor activity in response to that odor than saline controls. The increased motor responses were further potentiated in pups that experienced additional postnatal alcohol odor paired with tactile stimulation. In Experiment 2, pups were exposed to alcohol in the amniotic fluid 10 or 30 min prior to birth. As previously demonstrated the memory acquired in utero appears highly dependent upon contingency between exposure to this particular scent and delivery procedures. Pups in both prenatal treatment groups were then exposed to alcohol odor paired or unpaired with tactile stimulation. Some control animals received no further experience with either stimuli. Those pups exposed to alcohol odor paired with tactile stimulation both pre- and postnatally later showed maximum motor activity elicited by the odor of alcohol. The results support the notion of fetal associative learning comprising alcohol's chemosensory cues and behaviorally activating stimuli. Furthermore, the conditioned response under analysis is potentiated whenever neonates are reexposed to contingent presentations of the elements that defined the original associative memory.

Administration, Inhalation↗

Associative learning of odor with food- or blood-meal by Culex quinquefasciatus Say (Diptera: Culicidae).

The ability of many insects to learn has been documented. However, a limited number of studies examining associative learning in medically important arthropods has been published. Investigations into the associative learning capabilities of Culex quinquefasciatus Say were conducted by adapting methods commonly used in experiments involving Hymenoptera. Male and female mosquitoes were able to learn a conditioned stimulus that consisted of an odor not normally encountered in nature (synthetic strawberry or vanilla extracts) in association with an unconditioned stimulus consisting of either a sugar (males and females) or blood (females) meal. Such information could lead to a better understanding of the ability of mosquitoes to locate and select host and food resources in nature.

Animals↗

The role of CA3 hippocampal NMDA receptors in paired associate learning.

The hippocampus is necessary for declarative memory in humans and episodic memory in rodents. Considerable current research is focused on the role of plasticity within specific subfields of the hippocampus. Here, using a viral vector to temporally control a focal deletion of the NR1 gene, we show that learning novel paired associations between specific cues and their context is dependent on CA3 NMDA receptors. Deletion of CA3 NR1 genes in <30% of the dorsal hippocampus was sufficient to disrupt new learning, whereas the same treatment does not prevent expression of previously acquired paired associates and does not affect the ability to discriminate contexts or paired associate learning when either the cues or the context is familiar. The findings suggest that CA3 NMDA receptors specifically support the encoding of new experiences to involve incidental and contingent associations.

Animals↗

An individual differences analysis of ability and strategy influences: age-related differences in associative learning.

The relationships among abilities, strategies, and performance on an associative learning task were investigated for young (aged 17 to 34) and older adults (aged 60 to 82). Participants received extensive practice on a noun-pair task in which they could use a visual-scanning strategy or a memory-retrieval strategy. Older adults were more likely to use the scanning strategy. Age differences were reduced when comparisons were made only for participants using a retrieval strategy. Associative memory was predictive of learning on the task, and semantic memory access speed was predictive of practiced performance. Practiced performance on a memory-search task that also required associative learning was predictive of practiced noun-pair performance. Models of ability-performance relationships for skill acquisition are discussed.

Adolescent↗

Functional neuroanatomy of successful paired associate learning in Alzheimer's disease.

OBJECTIVE: The purpose of the study was to develop a strategy for functional imaging of neurodegenerative disorders that overcomes confounds associated with differential performance between patient and comparison groups. METHOD: Functional magnetic resonance imaging was used to examine responses to increasing difficulty of visuospatial paired associate learning in 12 patients with mild probable Alzheimer's disease and 12 age-matched healthy comparison subjects. Performance was matched across groups by only examining successful encoding and retrieval attempts. Adjustment for task difficulty was made on an individual basis so that the patients with Alzheimer's disease and the comparison subjects performed at the same relative levels of difficulty. RESULTS: A network of lateral and medial frontoparietal and occipital regions was engaged in all subjects during successful associative learning. As task difficulty increased, blood-oxygen-level-dependent responses increased linearly in occipitoparietal regions during encoding and retrieval. Differential activations in patients with Alzheimer's disease and comparison subjects were small and were found only when an uncorrected statistical threshold was used. CONCLUSIONS: By controlling for confounds of varying task difficulty and subsequent performance, remarkably similar brain activations were identified during successful paired associate learning in patients with Alzheimer's disease and in healthy comparison subjects. The study methods provide a useful model for further applications of functional imaging involving cognitive activation paradigms in the study of neuropsychiatric disorders.

Aged↗

Remodeling of hippocampal synapses after hippocampus-dependent associative learning.

The aim of this study was to determine whether hippocampus-dependent associative learning involves changes in the number and/or structure of hippocampal synapses. A behavioral paradigm of trace eyeblink conditioning was used. Young adult rabbits were given daily 80 trial sessions to a criterion of 80% conditioned responses in a session. During each trial, the conditioned (tone) and unconditioned (corneal airpuff) stimuli were presented with a stimulus-free or trace interval of 500 msec. Control rabbits were pseudoconditioned by equal numbers of random presentations of the same stimuli. Brain tissue was taken for morphological analyses 24 hours after the last session. Synapses were examined in the stratum radiatum of hippocampal subfield CA1. Unbiased stereological methods were used to obtain estimates of the total number of synapses in this layer as well as the area of the postsynaptic density. The data showed that the total numbers of all synaptic contacts and various morphological subtypes of synapses did not change in conditioned animals. The area of the postsynaptic density, however, was significantly increased after conditioning in axospinous nonperforated synapses. This structural alteration may reflect an addition of signal transduction proteins (such as receptors and ion channels) and the transformation of postsynaptically silent synapses into functional ones. The findings of the present study indicate that cellular mechanisms of hippocampus-dependent associative learning include the remodeling of existing hippocampal synapses. Further studies examining various time points along the learning curve are necessary to clarify the issue of whether these mechanisms also involve the formation of additional synaptic contacts.

Animals↗

Non-motor associative learning in patients with isolated degenerative cerebellar disease.

In recent decades it has become clear that the cerebellum is involved in associative motor learning, but its exact role in motor learning as such is still controversial. Recently, a contribution of the cerebellum to different cognitive abilities has also been considered, but it remains unclear whether the cerebellum contributes to cognitive associative learning. We compared nine patients with an isolated cerebellar degenerative disease in a cognitive associative learning task with 10 controls. Patients and controls were matched for age, sex, handedness, level of education, intelligence and capabilities of visual memory. The subjects were asked to learn the association between six pairs of colours and numerals by trial and error. Additionally, a simple reaction time and a visual scanning test were conducted in order to control for the influence of motor performance deficits in cerebellar patients. In comparison with the controls, it took the patients significantly longer to learn the correct associations between colours and numerals, and they were impaired in recognizing them later on. Two patients showed no associative learning effect at all. Neither the simple reaction time nor the visual scanning time correlated substantially with the results of associative learning. Therefore, motor-associated disabilities are unlikely to be the reason for the learning deficit in cerebellar patients. Our results suggest that the cerebellum might contribute to motor-independent processes that are generally involved in associative learning.

Aged↗

Marijuana influenced changes in GSR activation peaking during paired-associate learning.

Activation Peaking (AP) refers to a patterned physiological response occurring during learning. Marijuana has been found to interfere with both paired-associate learning and phasic GSR activity. Therefore, a study was performed to assess the effects of marijuana intoxication on paired-associate learning and concomitant GSR AP. Two marijuana usage categories were employed--light and heavy usage Ss. Within each category four groups were run in a design to test state-dependent effects. Each S was seen twice with a seven-day inter-session interval. The groups were P-P, P-M, M-M and P-M with P equals placebo and M equals 14 mg delta-9 THC. At each sessions S learned a nine-word paired-associate list to a criterion of one correct recitation, and then received 100 percent overlearning. No usage or group differences were found in level of basal conductance, except lights showed habituation over sessions and heavies did not. Magnitude of phasic GSR activation, aligned for AP, was significantly reduced for both heavy usage and marijuana intoxicated Ss. Also, only on placebo days was an AP effect evident. The results were discussed in terms of marijuana's effects on learning and physiology with emphasis on possible mechanisms of action.

Adolescent↗

Memory for temporal order and conditional associative-learning in patients with Parkinson's disease.

The performance of Parkinson's patients was compared to that of normal controls on memory for temporal order and conditional associative-learning tasks, each of which is sensitive to frontal-lobe dysfunction. Memory for temporal order involved reconstructing the presentation order of each of a series of drawings, words and designs. Recognition of similar stimuli was also examined. Parkinson's patients exhibited poor memory for the relative temporal relations between stimuli, though no group differences were observed in the number of stimuli placed in the correct position. Recognition was intact in the Parkinson's patients, and an absence of correlation between performance on the recognition and temporal order tasks indicates that the poor memory for temporal order is not simply a function of degraded memory for the individual stimuli. The conditional associative-learning task required subjects to learn, either by trial-and-error or with immediate correction, numbers paired with drawings, designs or spatial locations. Parkinson's patients were impaired only when learning by trial-and-error was required. Results suggest that the strategic retrieval processes involved in both memory for temporal order and learning conditional associations by trial-and-error depend on the integrity of the fronto-striatal system, which is known to be affected in Parkinson's disease.

Aged↗

Molecular kinetic modelling of associative learning.

Three molecular (enzyme) kinetic models have been designed that exhibit the basic properties of associative learning (classical conditioning). The enzyme systems are acted upon by an 'unconditioned' and a 'conditioned' ligand: temporally paired application of the two ligands leads to covalent enzyme modification, which serves as 'memory trace'. The behaviour of the systems has been investigated by computer simulation. Although the models are hypothetic, they do not contain biochemically inconceivable steps. The models demonstrate that already fairly simple molecular events may produce the phenomenology of associative learning.

Adenylyl Cyclases↗

Associative learning by locusts: pairing of visual cues with consumption of protein and carbohydrate

We investigated whether fifth instar African migratory locusts, Locusta migratoria could learn to associate visual cues with the macronutrient content of synthetic foods. During a 48-h training period, the insects had ad libitum access to two synthetic foods which were identical in all respects except that one lacked protein and the other lacked digestible carbohydrate. One food was placed at the end of a transparent Perspex cylinder which had been tinted green, and the other at the end of a yellow-tinted cylinder which was similar in all other respects. To obtain a balanced diet, the insects were thus forced to ingest the two macronutrients in visually different environments. Following this training period, they were then made selectively deficient in either protein or carbohydrate, before being tested for their tendency to enter, and the depth of entry into, yellow- or green-tinted cylinders that did not contain food. Locusts entered significantly more frequently the colour of cylinder that had previously been paired with the deficient nutrient (henceforth termed the 'training colour'). This was true irrespective of whether the nutrient was protein or carbohydrate, and whether the training colour was green or yellow. There was no effect of training on the average depth of entry into the cylinders. However, protein-deprived locusts penetrated significantly more deeply than carbohydrate-deprived locusts into both green and yellow cylinders, irrespective of the training colour. A separate experiment demonstrated that naive locusts entered more frequently into the yellow than the green side-arm, but there was no influence of colour on the depth of entry by naive locusts.Copyright 1997 The Association for the Study of Animal BehaviourCopyright 1997The Association for the Study of Animal Behaviour.

Journal Article↗

Learned association of allocentric and egocentric information in the hippocampus.

Single-cell recording was conducted in the hippocampus of rats that performed a spontaneous alternation task in a modified T-maze. In the central arm of the maze, 4 out of 45 cells (8%) were found that fired selectively depending on which turn the animals would take. This result is in disagreement with a previous study in which two-thirds of cells (22 out of 33) showed a clear bias for direction of turns. The interpretation was that the cells coded information of episodic memory. Our results do not support this hypothesis. Interestingly, over the course of training, an increasing number of cells were found that fired in correlation with the rats' movements. It is proposed that these cells associate egocentric motor information with allocentric spatial information rather than encode episodic memory.

Animals↗

Posttraining or pretest administration of nimodipine fails to affect retention of a simple learned association.

In previous experiments, the antagonist of voltage-sensitive calcium channels, nimodipine, given before training, enhanced the retention of an acquired preference for white-left relative to black-right in a two compartment apparatus. In the present experiments we attempted to determine if the retention effects produced by the drug could be attributed to effects occurring in the posttraining period. Various groups of rats received posttraining injections of nimodipine or its vehicle and two hours prior to testing received a second injection of nimodipine or its vehicle or no injection at all. All rats were tested for retention of the association twice, both 24 and 48 hr after acquisition. No posttraining or pretesting drug effects were found. This would support the view that the enhanced retention found after treatment with nimodipine found by ourselves and by others is due to a change in the animals at the time of acquisition.

Animals↗