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PubMed1989

Memory processes and aging: a defect of automatic rather than controlled processes?

The effect of age (20-86) and/or cultural level is investigated from the point of view of Cognitive Psychology. The study was carried out with 75 subjects distributed into 5 age-ranges and 3 cultural levels. It involved the following memory tests: forced choice recognition of faces (Warrington, 1984) and of abstract paintings; Rey Figure; immediate free recall; final free recall; learning and retention of paired associates; learning with AB-AC-AB design to test for interference; Selective Reminding test of Buschke (1973); repeated free recall. Data where analysed, taking into account dozens of variables. As far as age is concerned, all the analyses converge toward the same conclusion: short-term memory is not significantly affected by age, while a clear distinction appears between two kinds of secondary memory. Secondary memory involved in the course of learning or in the retention of learning is unaffected by age. By contrast, secondary memory involved in the retention of an initial or single confrontation with test material is very much affected by age. Age might, therefore, differentially affect two kinds of secondary memory. It is suggested that, contrary to the view of certain authors, age mainly affects automatic secondary memory, whereas voluntary, conscious, controlled and effortful secondary memory, which could require a greater amount of 'mental energy' or attentional resource, is relatively well preserved with age.

Adult↗

PubMed1996

Conditioned taste aversion in rats following intrathecal administration of contrast media.

PURPOSE: The occurrence of side-effects such as visceral malaise after intrathecal administration of the non-ionic radiography contrast media iomeprol, iopamidol, and iotrolan was assessed in rats by the conditioned tasted aversion procedure. METHODS: Reduced preference towards a saccharose solution compared with normal water following intraventricular administration of a contrast medium was used as a measure of the aversive response. RESULTS: At a dose of 100 mg I/kg none of the tested contrast media induced aversion. At 200 and 300 mg I/kg, both iopamidol and iomeprol induced significant aversive responses with respect to control, although the response of the iomeprol group appeared milder than that of the iopamidol group at a dose of 200 mg I/kg. Iotrolan could be tested only at the lowest dose since the high doses caused excessive mortality. CONCLUSION: Intrathecally administered iomeprol appeared to be well tolerated in rats at doses higher than those suggested for clinical use.

Animals↗

PubMed1998

Pure topographical disorientation related to dysfunction of the viewpoint dependent visual system.

A 70-year-old woman presented with pure topographical disorientation following haemorrhage in the right medial parietal lobe. She could not navigate in the real world despite good ability to draw maps, describe routes, and identify objects and buildings. Her performance on mental rotation, visual memory, and spatial learning tests also was normal. In contrast, she failed totally in a locomotor map test and in a task in which she was requested to judge viewpoints of buildings. Her highly selective topographical disorientation was probably caused by the inability to identify a viewpoint of a particular building. The lesion may have disconnected the association between the spatial information processed in the lateral parietal lobe and the visual memory mediated by the limbic system, which seems to be important for viewpoint dependent analysis.

Aged↗

PubMed2003

Increases in food intake or food-seeking behavior induced by GABAergic, opioid, or dopaminergic stimulation of the nucleus accumbens: is it hunger?

RATIONALE: Previous work has shown that stimulation of GABAergic, opioid, or dopaminergic systems within the nucleus accumbens modulates food intake and food-seeking behavior. However, it is not known whether such stimulation mimics a motivational state of food deprivation that commonly enables animals to learn a new operant response to obtain food. OBJECTIVES: In order to address this question, acquisition of lever pressing for food in hungry animals was compared with acquisition in non-food-deprived rats subjected to various nucleus accumbens drug treatments. METHODS: All animals were given the opportunity to learn an instrumental response (a lever press) to obtain a food pellet. Prior to training, ad lib-fed rats were infused with the gamma-aminobutyric acid (GABA)A agonist muscimol (100 ng/0.5 microl per side) or the mu-opioid receptor agonist D-Ala2, N-me-Phe4, Gly-ol5-enkephalin (DAMGO, 0.25 microg/0.5 microl per side), or saline into the nucleus accumbens shell (AcbSh). The indirect dopamine agonist amphetamine (10 microg/0.5 microl per side) was infused into the AcbSh or nucleus accumbens core (AcbC) of ad lib-fed rats. An additional group was food deprived and infused with saline in the AcbSh. Chow and sugar pellet intake responses after drug treatments were also evaluated in free-feeding tests. RESULTS: Muscimol, DAMGO, or amphetamine did not facilitate acquisition of lever pressing for food, despite clearly increasing food intake in free-feeding tests. In contrast, food-deprived animals rapidly learned the task. CONCLUSIONS: These findings suggest that pharmacological stimulation of any of these neurochemical systems in isolation is insufficient to enable acquisition of a food-reinforced operant task. Thus, these selective processes, while likely involved in control of food intake and food-seeking behavior, appear unable to recapitulate the conditions necessary to mimic the state of negative energy balance.

Amphetamine↗

PubMed2005

Neonatal lesion of forebrain cholinergic neurons: further characterization of behavioral effects and permanency.

Intraventricular injections of 192 IgG-saporin in the neonatal rat caused severe loss of basal forebrain cholinergic neurons and ectopic hippocampal ingrowths. These were evident at 24 months of age and thus, were lifelong consequences of the 192 IgG-saporin treatment. When tested as young adults on a novel water-escape radial arm maze, the rats with this lesion were slower to learn the task, committing significantly more working and reference memory errors before they achieved control level of performance. It is unlikely that this was a result of attentional impairment as the lesioned rats performed as vigilantly as controls in a five choice serial reaction time task. When tested in the Morris water maze at 22 months of age, they were slower at learning the hidden platform location. This contrasts with previous studies which have repeatedly shown that they normally acquire this task as young adults. It was concluded that this neonatal cholinergic lesion has modest but discernable effects on problem solving in young adulthood that are consistent with the reported effects of the lesion on cortical pyramidal neurons. The cognitive effects of the lesion may become more severe in aging, perhaps as a result of the added effects of aging on these neurons.

Acetylcholine↗

PubMed2006

Interfering with theories of sleep and memory: sleep, declarative memory, and associative interference.

Mounting behavioral evidence in humans supports the claim that sleep leads to improvements in recently acquired, nondeclarative memories. Examples include motor-sequence learning; visual-discrimination learning; and perceptual learning of a synthetic language. In contrast, there are limited human data supporting a benefit of sleep for declarative (hippocampus-mediated) memory in humans (for review, see). This is particularly surprising given that animal models (e.g.,) and neuroimaging studies (e.g.,) predict that sleep facilitates hippocampus-based memory consolidation. We hypothesized that we could unmask the benefits of sleep by challenging the declarative memory system with competing information (interference). This is the first study to demonstrate that sleep protects declarative memories from subsequent associative interference, and it has important implications for understanding the neurobiology of memory consolidation.

Adolescent↗

PubMed2000

Antidepressant-like effects of the subtype-selective nicotinic acetylcholine receptor agonist, SIB-1508Y, in the learned helplessness rat model of depression.

RATIONALE: Epidemiological studies of smokers suggest that there is a link between nicotine and depression. Nonetheless, few studies have examined the potential use of nicotinic ligands in the treatment of depression. OBJECTIVES: The goal of this study was to evaluate the effects of SIB-1508Y, a novel subtype-selective ligand for high affinity nicotinic acetylcholine receptors (nAChRs), in the learned helplessness model of depression in rats. METHODS: In this model, exposure to inescapable foot-shock produces a lasting deficit in escape responses emitted in a subsequent conditioned avoidance procedure (learned helplessness). The effect of SIB-1508Y on learned helplessness was compared to the clinically used antidepressants, imipramine and fluoxetine, and the non-selective nAChR ligand, nicotine. RESULTS: Similarly to imipramine and fluoxetine, subchronic treatment (5 days) with SIB-1508Y reversed the escape deficit in the learned helplessness model in a dose dependent manner. The effect of SIB-1508Y on learned helplessness was still apparent 1 week following drug administration and was also maintained after 4 weeks of daily administration. In contrast, while nicotine was able to attenuate the learned helplessness deficit, this trend only reached statistical significance after chronic administration. The non-competitive ion channel blocker mecamylamine increased escape failures when administered alone and blocked the effects of SIB-1508Y but not imipramine. SIB- 1508Y also produced an increase in avoidance responding, which suggests an enhancement of learning. CONCLUSION: These results not only suggest a role for nAChRs in the development of a depressive-like syndrome, but also that subtype-selective nAChR agonists, such as SIB-1508Y, may offer a novel therapeutic approach to the treatment of depression.

Animals↗

PubMed1995

Supplementary eye field contrasted with the frontal eye field during acquisition of conditional oculomotor associations.

1. The companion paper reported that a substantial proportion of cells in the supplementary eye field (SEF) of macaque monkeys show significant evolution of neuronal activity as subjects learn new and arbitrary stimulus-saccade associations. The purpose of the present study was to compare and contrast the activity of the SEF and the frontal eye field (FEF) during such conditional oculomotor learning. 2. In both SEF and FEF, we observed learning-dependent and learning-selective activity, defined as significant evolution of task-related activity as monkeys learned which of four saccades was instructed by a novel stimulus. By definition, in addition to changes as the monkeys learned the instructional significance of a novel instruction stimulus, learning-dependent activity also showed task-related modulation for trials instructed by familiar stimuli, whereas learning-selective activity did not. Of the 186 SEF neurons adequately tested, 81 (44%) showed one of these two categories of learning-related change. By contrast, of the 90 FEF neurons adequately tested, only 14 (16%) showed similar properties. This difference was highly statistically significant (chi 2 = 21.1; P < 0.001). 3. We also observed persistent differences in activity for trials with familiar versus novel instruction stimuli, which we termed learning-static effects. In some cases, the learning-static effect coexisted with learning-dependent or learning-selective changes in activity, although in others it did not. In the former cases, activity changed systematically during learning, but reached a level that differed from that for familiar stimuli instructing the same saccade. In the latter cases, the activity did not change significantly as the monkey learned new conditional oculomotor associations, but did show a significant difference depending upon whether a novel or familiar stimulus instructed a given saccade. Overall, 66 of 186 (35%) cells in the SEF and 17 of 90 (19%) cells in the FEF showed learning-static effects in one or more task periods. This difference was statistically significant (chi 2 = 7.9; P < 0.005). 4. The significant difference in the properties of SEF and FEF cells suggests a functional dissociation of the two areas during conditional oculomotor learning. In this respect, the FEF resembles the primary motor cortex, whereas the SEF resembles the premotor cortex.

Animals↗

PubMed1997

Visuospatial discrimination deficit in rats after ibotenate lesions in anteromedial visual cortex.

To assess the role of the rat anteromedial extrastriate cortex (AM) in a visuospatial discrimination task, restricted bilateral ibotenic acid lesions were placed stereotaxically in this region. Gray rats with lesions in AM were trained in a task requiring them to discriminate the location of a light stimulus placed vertically at different elevations. Correct responses required pressing right or left levers to obtain rewards. In contrast to unoperated controls, lesioned rats failed in learning the visuospatial discrimination task. A correlation was found between the bilateral extent of the lesion in area AM and the behavioral deficit. Another group of lesioned rats was trained to discriminate brightness differences of the light stimulus but requiring the same egocentric right/left motor response. The performance of these rats was similar to that of controls. From these results we conclude that extrastriate area AM in the rat is necessary for visuospatial discrimination, but not for correct egocentric motor responses. The visuospatial functions of area AM in the rat are reminiscent of visuospatial functions ascribed to the parietal streams of extrastriate visual areas in the monkey.

Animals↗

PubMed1996

The Morris water-escape task in mice: strain differences and effects of intra-maze contrast and brightness.

The Morris water-escape task is an extensively used experimental paradigm to assess the spatial discrimination performance and effects of brain lesions and drugs on this performance. In the first experiment, we compared the acquisition of this task by different strains (CFW1, BALB, NMRI, and C57BL) of mice and their performance in a probe trial. In a second experiment, C57BL mice were tested in Morris mazes where black and white tanks were combined with white or black platforms to investigate if and how the contrast between the tank and the platform affects the performance of the mice. In addition, four brightness conditions were compared to investigate whether or not the degree of brightness of the tank itself affects the learning performance. The results of these experiments indicated that 1. mice could readily learn the Morris task, 2. one of the contrast conditions affected the swimming speed, 3. the maze brightness per se did not affect water escape performance at all, and that 4. the swimming speed can strongly bias the outcome of Morris water-escape experiments in mice.

Animals↗

PubMed1998

Differences in active avoidance behaviour of hypoactive and hyperactive rats subjected to immobilisation stress.

Open field activity was studied in Wistar rats. Animals with low scores of ambulatory and rearing behaviours were grouped as hypoactive and those with high scores as hyperactive. Acquisition of active avoidance learning in a shuttle box was studied in the two groups. Hyperactive rats in contrast to hypoactive rats showed a better acquisition of avoidance learning. Learning was suppressed in both groups by domperidone, but was facilitated by immobilisation stress in the hypoactive group only. The two groups did not differ in the basal and stress evoked heart rates. These observations suggest that immobilisation stress favours enhancement of the dopaminergic related behaviour like avoidance learning in hypoactive rats.

Animals↗

PubMed1997

Neuromagnetic fields reveal cortical plasticity when learning an auditory discrimination task.

Auditory evoked neuromagnetic fields of the primary and association auditory cortices were recorded while subjects learned to discriminate small differences in frequency and intensity between two consecutive tones. When discrimination was no better than chance, evoked field patterns across the scalp manifested no significant differences between correct and incorrect responses. However, when performance was correct on at least 75% of the trials, the spatial pattern of magnetic field differed significantly between correct and incorrect responses during the first 70 ms following the onset of the second tone. In this respect, the magnetic field pattern predicted when the subject would make an incorrect judgment more than 100 ms prior to indicating the judgment by a button press. One subject improved discrimination for much smaller differences between stimuli after 200 h of training. Evidence of cortical plasticity with improved discrimination is provided by an accompanying decrease of the relative magnetic field amplitude of the 100 ms response components in the primary and association auditory cortices.

Acoustic Stimulation↗

PubMedDate not supplied

Evaluation of intrathecal contrast media by aversion conditioning in rats.

A method for quantification of aversion conditioning in rats was adapted to assess intrathecal neurotoxicity of contrast media (CM). Metrizamide, iopamidol, nonionic dimers DL-2-87 and DL-3-117, experimental iodophenyl glucose ethers DL-2-98 and DS-1-132, and Ringer's solution were injected into non-anesthetized rats drank water mixed with their preferred flavors, and subsequently were injected with 22.5 and/or 45 mgI/kg (200 and/or 400 mgI/ml concentration). From the intake of the preferred flavored water, expressed as percentage of total fluid intake consumed during a preference test and during a subsequent free choice test, a percentage avoidance/preference score was calculated as a measure of conditioning. At 12.5 mgI/Kg level, DL-2-87, which unexpectedly precipitated from solution in vivo, caused the most aversion, followed by metrizamide. The remaining compounds induced no significant aversion and were statistically indistinguishable from one another. At 45 mgI/kg dose level, all monomeric CM induced aversion of a statistically equal degree, while DL-3-117 proved nonaversive, equal to Ringer's solution.

Animals↗

PubMed1985

Deficits in non-spatial conditional associative learning after periarcuate lesions in the monkey.

Monkeys with lesions of the periarcuate region of the frontal cortex were severely impaired in learning a nonspatial conditional associative task. In this task, either one of two non-spatial responses (open the lit or the unlit box) was correct if emitted in the presence of the appropriate stimulus. In contrast, the periarcuate monkeys were able to learn, at a normal rate, the control tasks in which only one of the two responses was correct (e.g., go to the lit box), the animal's task being to emit this response when the cue to do so was given. These findings support the hypothesis that the periarcuate cortex is critically involved in conditional associative learning.

Animals↗

PubMed1997

Spatial memory impairment in rats with fornix transection is not accompanied by a simple encoding deficit for directions of objects in visual space.

In Experiment 1, rats learned 6 discriminations among pairs of complex wide-angle visual displays, presented concurrently, using a computer-controlled Y maze. Fornix-transected rats were unimpaired relative to controls regardless of whether the displays comprised a single large "objectlike" figure or "scenelike" arrays of spatially distributed figures. Experiment 2 compared 2 versions of a visual discrimination in which either object identity (independent of location within the visual field) or location within the visual field (independent of object identity) had to be used. The fornix-transected rats performed normally with either cue. In Experiment 3, however, the same group was clearly impaired on a standard spatial memory test, spatial delayed nonmatching to sample. Although the fornix-transected rats were more likely to choose rapidly and inaccurately, their deficit was not a by-product of impulsive responding. The spatial impairment was not merely a difficulty in encoding direction of a single item within visual space, but more complex configural deficits could not be ruled out.

Animals↗

PubMed1996

Effect of avian-human joint attention on allospecific vocal learning by grey parrots (Psittacus erithacus).

The authors studied whether grey parrots (Psittacus erithacus) would learn referential English vocalizations if training lacked full social interaction with humans. In previous studies, grey parrots learned human vocalizations most readily when training simultaneously demonstrated the meaning (full reference) and function (full contextual applicability) of the utterance and actively engaged the subject in learning (full interaction). Those studies, however, did not contrast effects of limited and full interaction or examine how interaction affects contextual applicability. Because an important factor in child language acquisition is joint attention-the social interaction between caretaker and human infant concerning objects and actions in their environment-the authors contrasted training in which joint attention was present or absent (i.e., full vs. limited interaction) and found that 2 parrots did not learn in the absence of joint attention but did learn English labels when full interaction was present.

Adult↗

PubMed1996

Functional mapping of human learning: a positron emission tomography activation study of eyeblink conditioning.

Regional cerebral blood flow (rCBF) was measured using positron emission tomography during eyeblink conditioning in young adults. Subjects were scanned in three experimental conditions: delay conditioning, in which binaural tones preceded air puffs to the right eye by 400 msec; pseudoconditioning, in which presentations of tone and air puff stimuli were not correlated in time; and fixation rest, which served as a baseline control. Compared with fixation, pseudoconditioning produced rCBF increases in frontal and temporal cortex, basal ganglia, left hippocampal formation, and pons. Learning-specific activations were observed in conditioning as compared with pseudoconditioning in bilateral frontal cortex, left thalamus, right medial hippocampal formation, left lingual gyrus, pons, and bilateral cerebellum; decreases in rCBF were observed for bilateral temporal cortex, and in the right hemisphere in putamen, cerebellum, and the lateral aspect of hippocampal formation. Blood flow increased as the level of learning increased in the left hemisphere in caudate, hippocampal formation, fusiform gyrus, and cerebellum, and in right temporal cortex and pons. In contrast, activation in left frontal cortex decreased as learning increased. These functional imaging results implicate many of the same structures identified by previous lesion and recording studies of eyeblink conditioning in animals and humans and suggest that the same brain regions in animals and humans mediate multiple forms of associative learning that give meaning to a previously neutral stimulus.

Adult↗

PubMed1991

Insular cortex and amygdala lesions differentially affect acquisition on inhibitory avoidance and conditioned taste aversion.

These experiments examined the effects of NMDA-induced lesions of the amygdala and insular (gustatory) cortex (IC) on inhibitory avoidance learning and conditioned taste aversion (CTA) in rats. IC lesions, but not amygdala lesions, disrupted CTA. In contrast, lesions of either brain region disrupted inhibitory avoidance learning. These findings support the view that the IC is strongly involved in the acquisition of external as well as visceral aversively motivated behavior. Despite extensive functional interconnections, these 2 brain regions appear to have different roles in mediating different forms of aversively based learning.

Amygdala↗