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Effects of morphine and heroin on discrimination learning and consolidation in mice.

Morphine and heroin were administered to mice learning to swim toward a light source (L procedure) or toward the dark (D procedure), in a Y water maze, under pre and post-trial drug treatment conditions. In the pre-trial experiments a clear disrupting effect on performance with the two procedures followed administration of both drugs, but for the L performance never fell below the 50% level of correct choices. Analysis of the performance within each session demonstrated a disruption in the long term memory consolidation mechanism. The administration of naloxone, or alternatively, discontinuation of the treatment, was followed by a gradual improvement, in performance by the treated animals. In both procedures, a performance disruption also followed the administration of the drugs immediately after each experimental session.

Animals↗

Strain differences in rewarded discrimination learning using the olfactory tubing maze.

We trained BALB/c Byllco (C), CD-1, SV 129/SvPasCr1 (129 SV), C57BL/6 (B6) and DBA/2J (D2) mice using the olfactory tubing maze with the hope of gaining insight into behavioral genetics related to learning and memory processes. All strains of mice acquired the odor-reward associations using this new task except the D2 strain. The C, CD-1, and 129 SV consistently remembered the associations from the sixth 20-trial training session, reaching 80% +/- 5 correct responses in session seven. The B6 mice required one more session to reach 76%, while the D2 mice never learned the correct odor-reward associations. All mice learned the paradigm and the timing of the task, although the 129 SV mice decreased slower the inter-trial intervals across sessions. With this new task, D2 mice, with a deficit totally devoted to an impairment on learning and memory, can be used as a model of hippocampal dysfunction, in some respects like that observed in human amnesic patients whose selective hippocampal-dependent memory is deeply impaired. The high-scoring strains (C, CD-1, and 129 SV) seem to be ideal in this task to study a gene-targeting mutation postulated to reduce behavioral performance, and inversely, for D2 mice. The moderate-scoring strain, B6, should be ideal for allowing gene-targeting to go either way. In addition, this new task, which enables automated training of odor associations, could be used for studying the phenomenon of transitivity in mice, as described in rats.

Animals↗

Direction discrimination learning in normal and visually deprived cats and the effects of lateral suprasylvian lesions.

We used 5 binocularly deprived cats (BD cats), 4 control cats reared also in the laboratory (C cats) and 4 cats reared in a normal environment (N cats). The cats were trained to discriminate an upward or downward-moving light spot versus a stationary spot (detection task) and then an upward versus a downward spot (direction task). The N and C cats learned slowly. The learning was slower than in previously studied discriminations of stationary stimuli. However, all N and C cats mastered the detection task and except one C cat the direction task. In contrast, 4 BD cats failed in the detection task and all in the direction task. This result is consistent with single-cell recording data showing impairment of direction analysis in the visual system in BD cats. After completing the training the upper part of the middle suprasylvian sulcus was removed unilaterally in 7 cats and bilaterally in 6 cats. Surprisingly, the unilateral lesions were more effective: the clear-cut retention deficits were found in 5 cats lesioned unilaterally, whereas only in one cat lesioned bilaterally.

Animals↗

Effects of nicotine on discrimination learning, consolidation and learned behaviour in two inbred strains of mice.

DBA/2J and C57BL/6J mice were injected with nicotine, and tested in a Y water maze in two procedures: the L procedure, coresponding to innate behavior, in which the animals must swim towards the light, and the D procedure, corresponding to the acquisition of a new pattern of behavior, in which they must swim toward the dark. Three sets of experiments were carried out: 1. In the pre-trial experiments, nicotine administration improved the innate tendencies of both strains, while the acquisition of a new behavior was facilitated in the C57 and impaired in the DBA mice. 2. In the post-trial experiments (D procedure), nicotine administration induced clear facilitating effects on the consolidation processes of the C57, while impairing these processes in the DBA strain. 3. The only effect evident, following nicotine administration, before the highest doses were reached, in the trained mice of both strains, was a performance impairment of the DBA mice trained in the L procedure.

Animals↗

Discrimination learning induced by training with identical stimuli.

Sensory stimuli become easier to detect or distinguish with practice. It is generally assumed that the task-relevant stimulus dimension becomes increasingly more salient as a result of attentively performing the task at a level that is neither too easy nor too difficult. However, here we show improved auditory frequency discrimination following training with physically identical tones that were impossible to discriminate. We also show that learning transfers across tone frequencies and across modalities: training on a silent visuospatial computer game improved thresholds on the auditory discrimination task. We suggest that three processes are necessary for optimal perceptual learning: sensitization through exposure to the stimulus, modality- and dimension-specific attention, and general arousal.

Acoustic Stimulation↗

Effects of chlorpromazine and imipramine on discrimination learning, consolidation, and learned behavior in two inbred strains of mice.

Chlorpromazine and imipramine were administered to DBA/2J and C57BL/6J mice swimming in a Y water maze toward a light source (L Procedure, corresponding to innate tendency) or towards the dark (D Procedure, corresponding to the acquisition of a new pattern of behavior). In two sets of experiments the drugs were administered to naive mice before and after each training session, respectively. In both strains, in the pretrial experiments, the innate tendencies were improved by both drugs; the acquisition of a new pattern of behavior was improved following imipramine but impaired following chlorpromazine. In the posttrial experiments (D procedure) the consolidation processes of both strains were improved following imipramine and impaired following chlorpromazine. In a third set of experiments imipramine was administered to previously trained mice of both strains and chlorpromazine to previously trained C57 mice. In both procedures the administration of increasing doses of both drugs was followed by a progressive lenghtening of the swimming times in the previously trained C57 mice; performance disruptions were evident in both procedures in trained DBA mice mice following imipramine.

Animals↗

Intelligence and motor skill acquisition by discrimination learning.

This experiment investigated the relation between intelligence and acquisition of motor skill using predictions from Zeaman and House's 1963 attention theory. 20 undergraduate students and 20 subjects of low IQ (WAIS-R Full Scale IQ range 50 to 73, M = 60) made linear positioning movements of long and short amplitude to the left and right of a central starting position. Four conditions (right-long, right-short, left-long, left-short) were created by specifying the corresponding target area on the positioning apparatus. One or both of the paired cues were varied, i.e., left, right, long, or short, while the dimensions of direction and amplitude remained unchanged across conditions. A shift from one condition to the next followed a criterion response of four consecutive movements to the target area. Results supported the hypothesis that subjects of low IQ would require more trials to criterion than subjects of normal IQ across all conditions of direction and extent. There was qualified support for the hypothesised interaction between intelligence and cue shifts. The practical implications and theoretical significance of these findings are discussed.

Adolescent↗

Hippocampal expression of the orphan nuclear receptor gene hzf-3/nurr1 during spatial discrimination learning.

The immediate-early gene hzf-3, also known as nurr1, is a member of the inducible orphan nuclear receptor family and is one candidate in the search for genes associated with learning and memory processes. Here we report that acquisition of a spatial food search task is accompanied by elevated levels of hzf-3 mRNA in the hippocampus. Adult male Long-Evans rats were handled, food-restricted, and allowed to habituate to the maze prior to training. During acquisition, rats were given one training session per day for 5 days. Each training session consisted of five trials in which animals searched the maze for food located in 4 of 16 holes in the floor of the maze. Training resulted in spatial acquisition of the task. Northern blot analysis showed significant increases in hippocampal hzf-3 mRNA 3 h after training in the maze. Next, brains were obtained from Naive, Habituated, Day 1, Day 3, and Day 5 animals and processed for in situ hybridization. The results showed significant increases of hzf-3 mRNA in CA1 and CA3 subregions of the dorsal hippocampus during acquisition of the task. We conclude that expression of the hzf-3 gene in the brain is associated with long-term spatial memory processes. The present results are the first to implicate an orphan nuclear receptor in long-term information storage in the hippocampus.

Animals↗

Dissociation of the effects of inferior temporal and limbic lesions on object discrimination learning with 24-h intertrial intervals.

Monkeys with bilateral ablations of the inferior temporal cortical area TE were trained on a visual discrimination task thought to measure non-cognitive habit formation. The task consisted of 20 object discriminations presented concurrently, but at the rate of only one trial on each per day; successive trials on a given discrimination were thus separated by 24-h intertrial intervals. Performance on this task by the animals with TE lesions was compared to that of both normal control monkeys and monkeys that had sustained bilateral removals of the amygdala and hippocampus. In contrast to the latter animals, which learned the 24-h intertrial interval task about as quickly as the normal controls, monkeys with area TE removals were markedly impaired. Taken together with earlier findings demonstrating that ablation of area TE impairs visual recognition memory, the present results suggest that area TE contributes not only, like limbic structures, to a cognitive memory system, but also, unlike limbic structures, to a non-cognitive habit system. Evidence is reviewed suggesting that this latter system may involve a corticostriatal circuit.

Animals↗

Enhanced spatial discrimination learning in rats following 5,7-DHT-induced serotonergic deafferentation of the hippocampus.

Learning in rats trained in the Stone 14-unit T-maze, a complex, positively reinforced spatial discrimination task was assessed following cytotoxic (5,7-dihydroxytryptamine; 5,7-DHT) deafferentation of the serotonergic inputs to the hippocampus. Serotonergic deafferentation was accomplished by infusing the cytotoxin in to the fornix-fimbria/cingulum bundle. Lesioned rats reached criterion (i.e. learned) in significantly fewer trials and made significantly fewer errors throughout training than either vehicle-injected or sham-operated controls. This represents the first time that the effects of selective chronic destruction of serotonergic inputs to the hippocampus have been investigated. The present results provide, therefore, evidence in support of a neuromodulatory role for serotonin (5-HT) within the rat hippocampus in the mediation of the processes underlying learning and memory for this task. Other studies are, therefore, warranted in order to determine whether hippocampal 5-HT also plays a role in the mediation of the processes underlying learning and memory in other types of tasks.

5,7-Dihydroxytryptamine↗

The role of visual field position in pattern-discrimination learning.

Invariance of object recognition to translation in the visual field is a fundamental property of human pattern vision. In three experiments we investigated this capability by training subjects to distinguish between random checkerboard stimuli. We show that the improvement of discrimination performance does not transfer across the visual field if learning is restricted to a particular location in the retinal image. Accuracy after retinal translation shows no sign of decay over time and remains at the same level it had at the beginning of the training. It is suggested that in two-dimensional translation invariance-as in three-dimensional rotation invariance-the human visual system is relying on memory-intensive rather than computation-intensive processes. Multiple position- and stimulus-specific learning events may be required before recognition is independent of retinal location.

Adult↗

Primary CA1 and conditionally immortal MHP36 cell grafts restore conditional discrimination learning and recall in marmosets after excitotoxic lesions of the hippocampal CA1 field.

Common marmosets (Callithrix jacchus, n = 18) were trained to discriminate between rewarded and non-rewarded objects (simple discriminations, SDs) and to make conditional discriminations (CDs) when presented sequentially with two different pairs of identical objects signifying reward either in the right or left food well of the Wisconsin General Test Apparatus. After bilateral N-methyl-D-aspartate (0.12 M) lesions through the cornu ammonis-1 (CA1) field (7 microl in five sites), marmosets showed profound impairment in recall of CDs but not SDs, and were assigned to lesion only, lesion plus CA1 grafts and lesion plus Maudsley hippocampal cell line, clone 36 (MHP36) grafts groups matched for lesion-induced impairment. Cell suspension grafts (4 microl, 15-25 000 cells/microl) of cells dissected from the CA1 region of foetal brain at embryonic day 94-96, or of conditionally immortalized MHP36 cells, derived from the H-2Kb-tsA58 transgenic mouse neuroepithelium and labelled with [3H]thymidine, were infused at the lesion sites. The lesion plus MHP36 grafts group was injected five times per week with cyclosporin A (10 mg/kg) throughout testing. Lesion, grafted and intact control marmosets (n = 4-5/group) were tested on recall of SDs and CDs learned before lesioning and on acquisition of four new CDs over a 6-month period. Lesioned animals were highly impaired in recall and acquisition of CD tasks, but recall of SDs was not significantly disrupted. Both grafted groups of marmosets showed improvement to control level in recall of CDs. They were significantly slower in learning the first new CD task, but mastered the remaining tasks as efficiently as controls and were substantially superior to the lesion-only group. Visualized by Nissl staining, foetal grafts formed clumps of pyramidal-like cells within the denervated CA1 field, or jutted into the lateral ventricles. MHP36 cells, identified by beta-galactosidase staining and autoradiography, showed neuronal and astrocytic morphology, and were distributed evenly throughout the CA1 region. The results indicate that MHP36 cell grafts are as functionally effective as foetal grafts and appear to integrate into the host brain in a structurally appropriate manner, showing the capacity to differentiate into both mature neurons and glia, and to develop morphologies appropriate to the site of migration. These findings, which parallel the facilitative effects of foetal and MHP36 grafts in rats with ischaemic CA1 damage, offer encouragement for the development of conditionally immortal neuroepithelial stem cell lines for grafting in conditions of severe amnesia and hippocampal damage following recovery from cardiac arrest or other global ischaemic episodes.

Animals↗

Influence of the suspension of continued treatment with flurazepam and amobarbital on two discrimination learning schedules.

The authors have studied the effect of the suspension of chronic treatment with flurazepam and amobarbital on the operant behavior of rats that for the first time were in the presence of two fixed-interval discrimination schedules. With the sound discrimination schedule, the responses emitted by the treated animals had charactistics similar to those of control animals. With the temporal discrimination schedule, though it is not possible to distinguish between learning rates, modifications in the intensity of the effect (increases in lever pressing) indicate that, considering the doses, the action of flurazepam is slight and that of amobarbital clear and statistically significant.

Acoustic Stimulation↗

Discrimination learning and extinction in paramecia (P. caudatum).

Prior attempts to condition a one-celled organism, paramecium, by either classical or instrumental procedures have yielded both positive and negative results. As the results of those studies may be subject to several interpretations other than one indicating learning, it was decided to use a more traditional technique for the present study. This experiment was designed to assess whether aversive electric shock could be used to train paramecia on a brightness discrimination task, a procedure that has been used in animal learning research. The results indicated that such learning may have occurred.

Animals↗

Role of the parahippocampal region in spatial and non-spatial memory: effects of parahippocampal lesions on rewarded alternation and concurrent object discrimination learning in the rat.

Rats with aspiration or excitotoxic (NMDA) lesions of the parahippocampal region were trained on a series of behavioral tasks which consisted of: (1) a test of spatial memory (discrete trial rewarded alternation), (2) a black-white discrimination, and (3) a test of non-spatial memory commonly used in primate models of amnesia (visual concurrent object discrimination). Rats in both lesion groups were severely impaired on the concurrent discrimination, even though they were able to learn the black-white discrimination normally. Animals with aspiration lesions were also impaired on the spatial memory task, whereas those with NMDA lesions did not differ from controls. The results indicate that concurrent object discrimination is a particularly sensitive measure of hippocampal/parahippocampal functions and suggest that these structures in the rat may serve mnemonic functions which are qualitatively similar to those of human and non-human primates.

Animals↗

Cue valence representation studied by Fos immunocytochemistry after acquisition of a discrimination learning task.

The piriform cortex (PCx) and related structures such as hippocampus and frontal cortex could play an important role in olfactory memory. We investigated their involvement in learning the biological value of an odor cue, i.e. predicting reward or non-reward in a two-odor discrimination task. Rats were sacrificed after stimulation by either rewarded or non-rewarded odor and Fos immunocytochemistry was performed. The different experimental groups of rats did not show strongly differentiated Fos expression pattern in either the PCx or the hippocampus. A few differences were noted in frontal areas. In the ventro-lateral orbital cortex, rats, ramdomly rewarded during the conditionning had a higher Fos level in comparison with other groups. In infralimbic cortex, rats, which learned the reward value of the olfactory cue and were water-reinforced the day of sacrifice, showed a higher Fos expression. Data are discussed in view of the olfactory learning paradigm and of the accuracy of the control groups used in the present experimental design. The behavioural conditions leading to Fos expression are further discussed since Fos is a marker of learning-induced plasticity as well as a general activity marker which can be activated by a wide range of stimuli not directly linked to memory.

Animals↗

Neural substrates of olfactory discrimination learning with auditory secondary reinforcement. I. Contributions of the basolateral amygdaloid complex and orbitofrontal cortex.

The basolateral amygdaloid complex (BLA) and orbitofrontal cortex (OFC) share extensive reciprocal connections, and interactions between these regions likely contribute to both mnemonic and affective processes. The present study examined the potential differential contributions of the BLA and OFC to performance of an olfactory discrimination task that incorporates auditory conditioned reinforcement and to expression of immediate post-shock freezing behavior. Damage to the BLA had little effect on performance of the conditioned reinforcement task but abolished immediate post-shock freezing behavior. In contrast, damage to OFC resulted in both a mild but significant performance decrement in the conditioned reinforcement task and a significant attenuation of immediate post-shock freezing behavior. These findings suggest that immediate post-shock freezing behavior is likely critically dependent upon interactions between the BLA and OFC. However, although mnemonic processes underlying accurate performance of the conditioned reinforcement task might be supported by OFC in part, such processes are independent of either the BLA or interactions between these two regions.

Acoustic Stimulation↗