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PubMed2006

Discrimination learning and reversal of the conditioned eyeblink reflex in a rodent model of autism.

Offspring of rats exposed to valproic acid (VPA) on gestational day (GD) 12 have been advocated as a rodent model of autism because they show neuron loss in brainstem nuclei and the cerebellum resembling that seen in human autistic cases . Studies of autistic children have reported alterations in acquisition of classical eyeblink conditioning and in reversal of instrumental discrimination learning . Acquisition of discriminative eyeblink conditioning depends on known brainstem-cerebellar circuitry whereas reversal depends on interactions of this circuitry with the hippocampus and prefrontal cortex. In order to explore behavioral parallels of the VPA rodent model with human autism, the present study exposed pregnant Long-Evans rats to 600 mg/kg VPA on GD12 and tested their offspring from Postnatal Day (PND26-31) on discriminative eyeblink conditioning and reversal. VPA rats showed faster eyeblink conditioning, consistent with studies in autistic children . This suggests that previously reported parallels between human autism and the VPA rodent model with respect to injury to brainstem-cerebellar circuitry are accompanied by behavioral parallels when a conditioning task engaging this circuitry is used. VPA rats also showed impaired reversal learning, but this likely reflected "carry-over" of enhanced conditioning during acquisition rather than a reversal learning deficit like that seen in human autism. Further studies of eyeblink conditioning in human autism and in various animal models may help to identify the etiology of this developmental disorder.

Analysis of Variance↗
PubMed1984

The role of response-reinforcer relationship in discrimination learning of mentally retarded persons.

The role of the spatial relationship between target responses and reinforcers in the discrimination learning of mentally retarded subjects was evaluated. On each training trial, subjects were instructed to move a hand-operated manipulandum to a positive stimulus located at the left or right end of a track. Correct responses were immediately followed by onset of a light and presentation of an edible reinforcer. In the control condition the light and edible reinforcers were presented in a single location equidistant from the ends of the manipulandum track; in the experimental condition, they were presented directly adjacent to the terminus of the response at the end of the manipulandum track corresponding to the location of the correct stimulus. Results showed that discrimination performance was more efficient in the experimental condition than in the control condition.

Adult↗
PubMed1988

The contribution of the rewarded and the non-rewarded stimulus in visual discrimination learning in mice.

The relative contribution of the rewarded and non-rewarded stimulus in the learning of a visual discrimination task in various species is unclear. A number of different parameters have been suggested as influencing the importance of the one over the other, among them the type of reinforcement. Our results show that with both positive reinforcement (using water as reward after a correct choice, and no reinforcement after an incorrect choice) and negative reinforcement (electroshock punishment after an incorrect choice) mice use the position of the incorrect stimulus as a cue for the discrimination. Mice trained by positive reinforcement without the added negative reinforcement of blocking the door on which the incorrect stimulus is projected, do not learn a brightness discrimination task. This suggested that the added negative reinforcement of the closed door had a strong influence on the learning behaviour in our experiments.

Animals↗
PubMed1977

Neurobehavioral and systemic effects of longterm blood lead-elevation in rats. I. Discrimination learning and open field-behavior.

In order to assess neurobehavioral deficit subsequent to early low-level lead-exposure, Wistar-rats were prenatally Pb-exposed via their mothers, neonatally via their dams' milk, and later on via their diet containing lead acetate (745 mg Pb/kg diet). Blood-lead levels (PbB) of dams increased from 24.2-31.2 microgram-% during pregnancy and suckling-periods, those of offsprings were 26.6 microgram-% at about 16 days of age and 28.5 microgram-% at about 190 days of age. Between 100 and 200 days of age 40 male offsprings were subjected to behavioral testing, namely an open field-test and a visual discrimination-learning task. Two learning-tasks of different complexity, i.e. orientation- and size-discrimination, were used. Data of 20 lead-treated animals were compared with those of 20 age-matched controls. In the open-field test lead-fed animals were significantly more restless than controls; an increase of ambulation, rearing and grooming was observed. In the difficult learning-task, i.e. size discrimination, only the controls did learn the problem, whereas only one of the lead-group did; there was, however, no difference between lead- and control-animals for the easy task, i.e. orientation-discrimination. The observed effects, namely overreaction in the open field and a deficit of visual discrimination learning, may be interpreted in terms of lead-induced CNS-dysfunction. They clearly suggest that the "no-response level" for neurobehavioral damage in the rat, subsequent to early lead-exposure, must be assumed to be lower than 35 microgram/100 ml.

Animals↗
PubMed1976

Differential effects of chlordiazepoxide on simultaneous and successive brightness discrimination learning in rats.

Chlordiazepoxide (CDP) at a dose of 20 mg/kg, i.p. was found to exert a marked disruptive effect on black-white successive discrimination learning in rats, while this effect failed to be obtained on black-gray simultaneous discrimination. Since trials to the learning criterion were found almost equal for saline rats on both successive and simultaneous discrimination tasks, the differential inhibitory effects of CDP could not be accounted for in terms of differences in difficulties of the two tasks. It is suggested that present results might be interpreted in terms of the hypotheses (a) that CDP produces a deficit in the integration of relevant stimulus cues when they were presented across trials or (b) that CDP has a disinhibitory effect in that inhibition of dominant response (positional preference) patterns is weakened by the drug, in a manner similar to effects observed in hippocampectomized animals.

Animals↗
PubMed1979

Discrimination learning in preschool children as a function of the stimulus and relevant dimension.

The purpose of the present study was to determine discrimination learning rates as a function of the nature of the stimulus and the relevant dimension. Ss were 160 preschool boys and girls. The design consisted of two stimuli (faces and cups), two constant dimensions (size and form), and two relevant dimensions (form and color when the size dimension was held constant, and size and color when the form dimension was held constant). The errors to criterion scores revealed that for cup stimuli the color dimension was learned more rapidly than size and form, while for face stimuli the dimensions of size and form were learned more rapidly than color.

Child, Preschool↗
PubMed1995

Effects of the Ca2+ channel antagonist flunarizine on visual discrimination learning.

Recent studies report that the peripheral administration of Ca2+ channel antagonists improves memory while central administration impairs memory in neurologically intact subjects. This study compares the effects of systemic versus central administration of the Ca2+ channel antagonist flunarizine on visual discrimination learning. In Experiment 1, 60 five-day-old male chicks received an intraperitoneal injection of 0, 1, 10, or 25 mg/kg flunarizine. Each chick then received three post-treatment test sessions (+5 min, +30 min, and +24 h) consisting of 60 visual discrimination trials followed by 5 min of observation in an open field. Flunarizine produced a dose- and time-dependent facilitation of learning. Evaluation of open-field behaviors indicated that the dose of flunarizine required to increase spontaneous activity was 10 times higher than the dose required to facilitate visual discrimination learning. No other open-field behaviors were effected. In Experiment 2, 44 chicks received intracerbroventricular injections of 0, 100 nM, 100 micro M, or 1 mM flunarizine followed by visual discrimination training as described in Experiment 1. Ventricular injection of flunarizine significantly increased the number of errors made during acquisition and retention trials. These data are consistent with earlier studies showing that systemic, but not central, administration of Ca2+ channel antagonists facilitates learning.

Animals↗
PubMed2004

Fornix lesions impair context-related cingulothalamic neuronal patterns and concurrent discrimination learning in rabbits (Oryctolagus cuniculus).

Cingulothalamic neurons develop topographic patterns of cue-elicited neuronal activity during discrimination learning. These patterns are context-related and are degraded by hippocampal lesions, suggesting that hippocampal modulation of cingulothalamic activity results in the expression of the patterns, which could promote the retrieval of context-appropriate responses and memories. This hypothesis was tested by training rabbits (Oryctolagus cuniculus) with fornix lesions concurrently on two discrimination tasks (approach and avoidance) in different contexts. Because the same conditioned stimuli were used for both tasks, contextual information was critical for overcoming intertask interference during concurrent task acquisition. The lesions degraded the topographic patterns and significantly impaired concurrent learning, suggesting that hippocampal-cingulothalamic interactions and the resulting topographic patterns are critical for processing contextual information needed to defeat interference.

Action Potentials↗
PubMed1994

Conditioned manipulation of natural killer (NK) cells in humans using a discriminative learning protocol.

There is growing evidence indicating that the immune function can be modified by classical conditioning techniques. This phenomenon, initially explored in animals, is further documented by studies providing evidence that the human immune response can also be influenced by classical conditioning processes. In the present study, we tested the hypothesis that human immune parameters can be modulated by discriminative learning processes. Using a classical discriminative conditioning design, healthy volunteers were provided with a CS+ (sherbet sweet/white noise), which was repeatedly paired with an injection of epinephrine (unconditioned stimulus, US). After epinephrine injections (0.2 mg subcutaneously), a transient increase of natural killer (NK) cell activity (unconditioned response, UR) could be observed. A second stimulus complex (herbal sweet/auditory stimulus, conditioned stimulus, CS-) remained without reinforcement. After repeated presentation of the stimuli, re-exposure of the CS+ on the test trial 1 resulted in a significantly increased number of NK positive (NK+) cells and in slightly elevated NK cell activity. No alteration of NK cells, however, could be observed after presentation of the CS-. A second re-exposure of the CS+ on test trial 3, again resulted in a marked increase of NK+ cell number as well as in significantly elevated NK cell activity. The data presented here extend previous observations of conditioned alteration of immune responses in humans and indicate that the human organism might be able to react differentially to external stimuli, which have been associated with different immunological consequences.

Adult↗
PubMed2003

Neural encoding in ventral striatum during olfactory discrimination learning.

A growing body of evidence implicates the ventral striatum in using information acquired through associative learning. The present study examined the activity of ventral striatal neurons in awake, behaving rats during go/no-go odor discrimination learning and reversal. Many neurons fired selectively to odor cues predictive of either appetitive (sucrose) or aversive (quinine) outcomes. Few neurons were selective when first exposed to the odors, but many acquired this differential activity as rats learned the significance of the cues. A substantial proportion of these neurons encoded the cues' learned motivational significance, and these neurons tended to reverse their firing selectivity after reversal of odor-outcome contingencies. Other neurons that became selectively activated during learning did not reverse, but instead appeared to encode specific combinations of cues and associated motor responses. The results support a role for ventral striatum in using the learned significance, both appetitive and aversive, of predictive cues to guide behavior.

Action Potentials↗
PubMed1989

Conditioned taste aversions as a behavioral baseline for drug discrimination learning: an assessment with phencyclidine.

When PCP was given prior to the pairing of saccharin with LiCl (and the PCP vehicle prior to a nonpoisoned exposure to the same saccharin solution), rats rapidly acquired the discrimination, avoiding saccharin consumption following PCP and consuming saccharin following the vehicle after only three conditioning trials. Conversely, when the PCP vehicle was given prior to the saccharin-LiCl pairing and PCP prior to a nonpoisoned exposure to saccharin, other subjects avoided saccharin consumption following the vehicle injection and readily consumed saccharin after an injection of PCP. During dose substitution sessions, animals displayed greater drug-appropriate responding as the dose of PCP increased. When a range of doses of ketamine was given in place of PCP prior to saccharin access, subjects displayed dose-dependent PCP-appropriate responding. When a range of doses of d-amphetamine was substituted for PCP, subjects displayed vehicle-appropriate responding at all doses. The relative efficacy of the taste aversion procedure as a baseline for drug discrimination learning is discussed.

Animals↗
PubMed1995

Visual discrimination learning in spontaneously hypertensive (SHR) and Wistar normotensive rats: computerized analysis of choice strategies.

Spontaneously hypertensive rats (SHR) were found to learn a visual discrimination paradigm better than Wistar normotensive rats (NT). The present analysis of choice strategies used by rats was performed to detect possible correlates between patterns of responding and duration of learning. The following strategies were included into the analysis: perseveration and alternation of choice (response-set hypotheses), win-stay lose-shift and win-shift lose-stay (prediction hypotheses). A computer programme called "The Thinking Rat" was written to analyse rat strategies during the learning. The analysis was applied for two irrelevant dimensions of stimuli, i.e. position and orientation, and for colour as a relevant cue. SHR solved the task using different strategies than the NT rats. All subjects began by responding to position as a cue, but SHR gave up this strategy more quickly than NT rats did and responded earlier to colour. NT rats showed a strong preference to persevere in their choices with respect to stimulus position, whereas SHR used more frequently the prediction hypotheses with respect to colour. The analysis of performance and the analysis of choice strategies-could indicate that the discrepancy in learning between SHR and NT rats may be caused by differences in attention.

Analysis of Variance↗
PubMed2002

Effect of chronic inhibition of calpains in the hippocampus on spatial discrimination learning and protein kinase C.

Several behavioral and electrophysiological studies have suggested that a sustained activation of protein kinase C would be required to underlie persistent changes associated with memory formation. Limited proteolysis of PKCs by calpains, calcium-activated proteases, cleaves the catalytic and the regulatory domains, generating a free catalytic fragment termed PKM, constitutively active. In order to investigate the potential physiological importance of this limited proteolysis as a mechanism of PKC activation, we have studied the effect of the calpastatin peptide, a specific calpain inhibitor, on the learning of a spatial discrimination task in a radial maze. Thus, using osmotic micro-pumps, the calpastatin peptide was infused bilaterally into the dorsal hippocampus during the six sessions of training and the probe test. The treatment was shown to facilitate the performance of the mice on the two last training sessions and on the probe test. This behavioral effect was shown to correspond to the reduced calpain activity observed in the hippocampus at the very end of the 7-day infusion of the calpastatin peptide, suggesting a relation between both events. In addition, PKC activity measured immediately after the probe test was notably decreased in the membrane fraction of the hippocampus. Although protein levels of PKCs and calpains quantified by western blot were not affected by calpastatin infusion, we found a noticeable correlation between mu-calpain and PKCgamma levels confirming the particular relationship between both proteins. These results suggest that calpains influence on PKCs activity may affect cellular mechanisms during memory processes.

Animals↗