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PubMed2004

The neural mechanisms of object working memory: what is where in the infant brain?

The question of how representational capacities develop in humans has been engaging cognitive psychologists for decades. Looking time studies have explored when infants start to show signs of perceiving and remembering the properties of specific objects at specific locations. Here we integrate these findings into the neuroscientific framework of human visual working memory. We suggest that the development of a system involving the temporal cortex, thalamic and hippocampal structures and possibly the dorsolateral prefrontal cortex (later in development) can account for these behavioral results. Our explanation differs from most of the current approaches in developmental science as we put less emphasis on the contribution of lateral prefrontal areas. We discuss shortcomings of the theories that propose a functional subdivision of these areas and their difficulty in accounting for results from monkey lesion and infant studies. We believe that this shift in focus is desirable both in light of what recent results on medial temporal lobe processing reveal about object working memory, and given how well these results fit the behavioral developmental data.

Animals↗
PubMed1999

Behavioral changes in transgenic mice expressing both amyloid precursor protein and presenilin-1 mutations: lack of association with amyloid deposits.

Mutations in the amyloid precursor protein (mAPP) and in presenilin 1 (mPS1) have both been linked to increased production of the beta-amyloid peptide (A beta). Doubly transgenic mice produced by mating of a parental line carrying the "Swedish" (K670N/M671L) APP mutation with a FAD4 (M146L) mutant presenilin 1 line developed numerous fibrillar A beta deposits by 6 months of age. Prior work demonstrated that mAPP and doubly transgenic (mAPP/mPS1) mice have deficits in Y-maze alternation behavior as early as 3 months of age. Increased activity was also apparent in the mAPP/mPS1 mice at this time point. These changes in Y-maze performance persisted in mAPP/mPS1 mice at 6 and 9 months of age. The mPS1 singly transgenic mice were not impaired on this task at any age. Six- and nine-month-old mice were also tested for spatial navigation behavior in the Morris water maze. In training trials, no differences in escape latency were detected among the four genotypes. In probe trials, no differences were detected in either the time spent in the trained quadrant or the number of platform crossings among the four groups. Histological staining for A beta amyloid deposits indicates that all doubly transgenic mice have amyloid deposits by 6 months of age (roughly 25 mice examined thus far), yet no 3-month-old mice have been found with deposits. A beta immunostaining confirmed that the 9-month-old mice tested behaviorally also have A beta deposits. Thus, doubly transgenic mice exhibited changes in Y-maze performance prior to the formation of amyloid deposits, which are essentially unchanged as the deposits increase in number and size to 9 months of age. Yet these mice fail to reveal impairments in spatial navigation at 6 or 9 months in spite of the increasing plaque burden. These data indicate that A beta deposits alone are not sufficient to cause robust spatial memory impairment in mice of this mixed background lineage and age.

Alzheimer Disease↗
PubMed2003

The study of spatial memory in adult male rats with injection of testosterone enanthate and flutamide into the basolateral nucleus of the amygdala in Morris water maze.

Extensive evidence suggests that the amygdala is involved in memory. The presence of androgenic and estrogenic receptors in the amygdala may reflect a possible involvement in certain activities of this part of the brain. Since sex steroids are known to play role in the maintenance and modulation of behavior, particularly spatial cognition throughout the life span, it was interesting to explore the role of these receptors in spatial memory. Therefore, an experiment was designed to investigate the effect of testosterone enanthate as an agonist and flutamide as an antagonist of androgenic receptors on spatial memory and learning. Wistar rats were bilaterally cannulated into basolateral nucleus of amygdala. Animals in different groups including vehicle (dimethyl sulfoxide) were proven to be inert for memory and learning. Testosterone enanthate (20, 40, 80 and 120 microg/0.5 microl), and flutamide (2, 5, 10, 20 and 40 microg/0.5 microl) were injected in both cannulae 30 min before each training day. After 4 days of experiments, results indicate a dose-dependent increase in parameters of escape latencies and travel distances to find the invisible platform in the group that received 120 microg/0.5 microl testosterone enanthate as compared to the control and vehicle groups. Flutamide had no effect on spatial memory. Therefore, it appears that androgens may effect memory and learning in amygdala. This is a feature that requires further investigation.

Amygdala↗
PubMed2005

Effects of vibrissae removal on search accuracy in the water maze.

In two experiments, the vibrissae were clipped on either the left, the right, or both sides, and the rats were trained to find a submerged platform in the Morris water maze. In both experiments, animals without vibrissae on both sides or on the left consistently spent significantly more time in the "counter" area twice the platform diameter in size, surrounding the submerged platform, than intact controls. Counter preference was not as consistent across experiments in rats with right vibrissae removed. These results suggest that the vibrissae are required for proprioceptive location of the platform itself, but not for proximal search accuracy. Since ischemic damage to hippocampal CA1 pyramidal cells has also been reported to prolong counter search during training, the results support the suggestion that impaired hippocampal processing of proprioceptive information from the vibrissae may contribute to the increased latency to find the platform shown by ischemic rats.

Analysis of Variance↗
PubMed2004

Exercise, but not environmental enrichment, improves learning after kainic acid-induced hippocampal neurodegeneration in association with an increase in brain-derived neurotrophic factor.

Previous studies have suggested that exercise in a running wheel can be neuroprotective, perhaps due to, among others, gene-expression changes after exercise, increases in trophic proteins and/or enhanced cardiovascular responsivity. Here we ask whether physical exercise or environmental enrichment provide protection after brain damage, especially in terms of recovery of cognitive function. To evaluate the neuroprotective effect of these conditions, we used the kainic acid (KA) model of neuronal injury. Systemically-administered KA induces excitotoxicity by overstimulation of glutamate receptors, resulting in neuronal death by necrosis and apoptosis. Our results show that exercise, but not enriched environment, prior to KA-induced brain damage, improved behavioural performance in both Morris watermaze and object exploration tasks. However, prior exercise did not decrease to control levels the hyperactivity normally seen in KA-treated animals, as measured by ambulation in the open field. Furthermore, both exercise and enriched environment did not protect against neuron loss in CA1, CA2 and CA3 areas of the hippocampus, despite a substantial increase in brain-derived neutrophic factor (BDNF) levels in dentate gyrus of the exercise and KA-treated animals.

Analysis of Variance↗
PubMed2005

Anti-craving drugs acamprosate and naloxone do not reduce expression of morphine conditioned place preference in isolated and group-housed rats.

Relapse prevention in clean addicts is a great challenge for addiction-therapy. As strong cravings often precede relapse, anti-craving drugs seem to be a promising way for addicts to stay clean. Naloxone and acamprosate are two candidates for anti-craving drugs that are already used for relapse prevention in alcoholic patients. However, it has to be figured out if both drugs are also effective in opiate-addicts. In order to evaluate their effectiveness, a conditioned place preference (CPP) paradigm was used in rats conditioned to 10 mg/kg, i.p., morphine. As acamprosate and naloxone have been suggested to selectively affect different types of craving (withdrawal-craving versus reward-craving), we have tried to modulate craving-behaviour by maintaining two groups of rats under different conditions (isolated versus group-housed). Thereafter, the effectiveness of acamprosate (200 mg/kg, i.p.) and naloxone (2 mg/kg, i.p.) in reducing morphine-CPP expression was evaluated. As a result, isolation produced a weak reduction in morphine-CPP development. Furthermore, acamprosate and naloxone had no effect on morphine-CPP expression. Based on the present results, we assume that the anti-craving drugs acamprosate and naloxone may not be effective for relapse prevention in opiate-addicts.

Acamprosate↗
PubMed1998

Development of a transient increase in recurrent inhibition and paired-pulse facilitation in hippocampal CA1 region.

Paired-pulse recurrent inhibition (RI) of population spike (PS) and facilitation (PPF) of field excitatory postsynaptic potential (EPSP) were studied in the CA1 region of hippocampal slices taken from Wistar rats aged from 9 days to 16 months. The comparison of three different paired-pulse protocols revealed the antidromic-orthodromic (A-O) stimulation as the most reliable in quantifying the strength of fast (peaking at 10 ms) and slow (peaking at 200 ms) components of recurrent inhibition. Fast RI, present but weak at 9 days, progressively increased to reach its maximal strength at 30 days, declining in adult (2 m) and middle-aged (16 m) animals. Slow RI was replaced by facilitation at 9 days while it was absent at 15 days. It reached adult values at 30 days. A reduction of the test response at interpulse interval (IPI) of 2-4 ms was strong in developing and adult animals, but was significantly decreased in 16 m. At maximal stimulation PPF was expressed as an enhancement of the slow rather than the fast phase of the EPSP and was particularly strong with a prominent N-methyl-D-aspartate dependent component. A very characteristic selectivity for a prominent PPF at stimulation frequency of 5 Hz appeared first at the 18th day and increased gradually to reach a maximum at the 30th day, after which it declined to very low values in middle-aged animals. A similar developmental pattern was observed in slices taken from rats reared in complete darkness, suggesting a strong innate origin. The ability of hippocampal circuits for plastic gating of information appears to be transiently enhanced at the completion of the first postnatal month as it can be exercised at a wider part of the frequency spectrum, with maximal inhibition and potentiation especially at the frequency of theta rhythm.

Age Factors↗
PubMed1995

Comforting: exploring the work of cancer nurses.

In a study to identify and describe nurses' use of comforting strategies, techniques of qualitative ethology were used to analyse videotaped recordings of nurse-patient interactions on an active cancer treatment ward. Comforting strategies nurses were observed to use included gentle humour, physical comfort measures, emotionally supportive statements, and comforting and connecting touch. In addition they increased physical proximity, provided patients with information, supported patients' active participation in decisions regarding their care, and offered opportunities for patients to engage in social exchange. These strategies appeared to play a major role in helping cancer patients endure the discomforts associated with their illness and/or treatment. Various combinations of comforting strategies were used in four different contexts, including: helping patients put experiences into perspective; helping them stay in control; providing opportunities to function as normally as possible; and providing emotional support. The findings of this study support conceptualizations of comforting that extend beyond measures related to symptom control and indicate that comforting strategies used by cancer nurses comprise a significant part of their work.

Adaptation, Psychological↗
PubMed2001

Adrenergic hyperactivity and metanephrine excess in the nucleus accumbens after prefrontocortical dopamine depletion.

Selective dopamine depletion within the medial prefrontal cortex in rats is known to enhance dopamine and norepinephrine levels in the nucleus accumbens and to induce characteristic behavioral disturbances. The present study was designed to determine levels of adrenaline, apart from dopamine and norepinephrine, and metabolites in the nucleus accumbens after prefrontocortical dopamine depletion. Prefrontocortical dopamine depletion was carried out by injecting 6-hydroxydopamine, and it was validated through: the emergence of behavioral disturbances such as amphetamine-induced stereotypies, spontaneous motor hyperactivity, and enhanced "anxiety-like" responses and through postmortem quantification of catecholamine levels by using high-performance liquid chromatography. The findings indicated that lesioned rats exhibited more oral stereotypies after amphetamine, were hyperlocomotive, and showed more pronounced anxiety-like behaviors than controls. Following prefrontocortical dopamine depletion, postmortem concentrations of dopamine and norepinephrine, along with the metabolites 3,4-dihydroxyphenylacetic acid and vanillylmandelic acid, were reliably enhanced in the nucleus accumbens as expected, and dopamine turnover was decreased. Furthermore the nucleus accumbens contained higher levels of adrenaline and its transmethylated metabolite metanephrine. To sum up, prefrontocortical dopamine depletion induces motor and emotional disturbances in rats and alters the neurochemical profile of the nucleus accumbens, not only inducing dopaminergic and noradrenergic hyperactivity but also leading to adrenaline and metanephrine excess.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Memory related role of the posterior cholinergic system.

In order to establish a model for the possible neuropathology of patients with Alzheimer's disease, various behaviors of rats with different chemical lesions in cholinergic regions were studied and compared with those of sham-operated control rats. A battery of neurological tests was used as well as activity measurements and two learning tasks: a positively reinforced place-learning task with delay periods of Os, 1 min, 15 min, and 2h, and a shock-motivated two-way active avoidance task. While in general no intergroup differences were obtained in performance on the neurological test battery or the rats' activity in an open field, there were marked impairments in the three lesioned groups compared to the control group in the two learning tasks. These deficits were less severe in the two groups with lesions of the medial septal/vertical diagonal band of Broca region and the nucleus basalis of Meynert region, but rather marked in the group with lesions of neurons situated in the pontomesencephalic region, although the amount of ibotenic acid injected had been the same for all groups. We conclude from these data that changes in mesencephalic cholinergic regions might play a significant role in the pathology of Alzheimer's disease. The existence of such regions was recently established for primates as well, thus providing a basis for justifying an animal model of this human disease.

Alzheimer Disease↗
PubMedDate not supplied

[A chamber for evaluating the free choice by laboratory rats and mice of a space containing tobacco smoke].

An original experimental setup has been designed that allows evaluation of the free preference of space containing tobacco smoke by small laboratory animals. For the laboratory mice (C57B1/6 and BALB/c) and rats (MNRA and MR) placed every day into this box, no emotional-stress reaction (ESR) caused by the environment novelty was observed on the 19th day of experiment. A difference in the free preference of space containing tobacco smoke was observed between inbred animals with active and passive ESR phenotypes.

Animals↗
PubMed2005

The cell recognition molecule L1 and cognition.

Cell adhesion molecules were classically known to be key players in a whole array of biological functions during development through cell-cell and cell-substratum adhesion. Accumulating evidence suggests, however, that the functional significance of adhesion molecules may extend well beyond embryonic development into adult stage. The aim of this article is to review our current knowledge on the implications of adhesion molecules in various cognitive processes. Particular emphasis was placed on the immunoglobulin superfamily of adhesion molecules, which are found to be involved in activity-dependent plasticity of the nervous system, and hence promising candidates in modulating cognitive functions.

Animals↗
PubMed1983

A multivariate approach to the analysis of genetic and septal lesion effects on maze performance in mice.

Reported are univariate and multivariate analyses concerning spatial discrimination behavior of Binghamton heterogeneous (HET) stock, C57BL/6J, and RF/J mice that had received either septal lesions or control surgery. In acquisition of an appetitively motivated T-maze task, lesions impaired HET but improved RF performance relative to their respective controls. When mice with lesions were reversed on a spatial discrimination acquired in a 17 degrees C water maze their performance was worse than control animals; the magnitude of the deficit was strain-specific. Measures of reactivity to handling suggested that HET and RF mice with lesions were more reactive than their control counterparts, while there was no such difference in C57 mice. Multivariate approaches broadly corroborated the importance of many complex Gene X Environment interactions that mold experience and thus behavior. In addition, they appeared to give some potentially important insights into the differential "behavioral profiles" of mice with lesions and control mice of the three genotypes; for instance, reactivity to handling and repeated error measurements were important variables in discriminating among the various groups in both learning tasks. The need to establish better and more stable behavioral profiles is clear; thus, multivariate techniques should be considered as useful, additional tools for the development and evaluation of explanatory theories regarding functions of central nervous system regions.

Animals↗
PubMed2004

Medial prefrontal cortex and precision of temporal discrimination: a lesion, microinjection, and microdialysis study.

In this paper, we examined the role of the medial prefrontal cortex in temporal discrimination in three experiments using rats. Experiment 1 attempted to dissociate the roles of the medial precentral (PrCm) area from the prelimbic and infralimbic (PL-IL) area in temporal discrimination using fixed-interval (FI) schedule. The gradient of response rate distribution became more moderate by a lesion of the PrCm, but not by a lesion of the PL-IL. In experiment 2, the efflux of acetylcholine (ACh) in the PrCm area during temporal discrimination tasks was compared to that during non-temporal discrimination tasks. ACh efflux was not different between these two tasks. In experiment 3, microinjection of the anticholinergic drug scopolamine (10 microg) into the PrCm area made the gradient of response rate distribution moderate. These findings suggest that reduced activity of the ACh system within the PrCm area impairs the precision of temporal discrimination, even though enhancement of this system is not indispensable for performing temporal discrimination.

Acetylcholine↗