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R Jaffard

Publications and source records attributed to R Jaffard.

At least 73 records · Page 4Linked to original sources

[Demonstration of dissociation between frontal and temporal lesions in man on two versions of delayed non-matching recognition tests used in monkeys].

11 patients with frontal lobe lesions (F group), 9 patients with temporal lobe lesions (T group) and 18 normal control subjects (C group) were tested on two versions of the delayed non matching-to-sample task using either different pairs (DNMTS) or the same pairs of objects (RECURRENT) on successive test trials. The results revealed that the DNMTS task was sensitive to memory impairment but did not differentiate the two experimental groups. In contrast, the recurrent version of the task showed a dissociation between the two pathologies. Thus, whereas patients of group T exhibited an accelerated rate of forgetting as a function of the retention interval, patients of group F were impaired whatever the retention interval.

Adult↗

Effects of chronic ethanol consumption associated or not with experimental anterior thalamic lesions on spontaneous sequential alternation in mice.

Previous studies from our team have shown that a 12 month ethanol administration induced deficits in a sequential alternation task, whereas a 6 month treatment had no effects. We have already shown that the 12 month treatment induced deficits both in diencephalic and hippocampal structures, whereas the 6 month treatment damaged only the mammillary bodies. Thus, the question remained whether or not increasing selectively the diencephalic damage by lesioning the anterior thalamic nuclei would disrupt sequential alternation in 6 month ethanol-treated mice. Results indicate that alcohol-treated mice exhibiting experimental lesions into the anterior thalamus were significantly impaired in the sequential task as compared to both controls or 6 month ethanol-treated mice. In contrast, anterior thalamic lesions in normal (no alcohol treatment) subjects induced no deficits. The relative contribution of the hippocampo-mammillo-thalamic circuitry in sequential alternation is discussed.

Afferent Pathways↗

[Effects of tianeptine on learning and memory in mice. Improvement of impairments induced by chronic alcoholism and brain aging].

Tianeptine, a molecule with antidepressant properties, was found to affect certain learning and memory impairments induced by chronic alcoholism and aging in the mouse. Impairment in spontaneous alternation induced by chronic (12 months) alcohol intake and accelerated loss of spatial learning skills related to aging disappeared totally after administration of tianeptine (10 mg.kg-1). In certain situations (discrimination acquisitions), tianeptine was uneffective in older animals at this dosage, but had a facilitating effect in young animals. The effects of tianeptine on serotonin mediated transmission and the probable implication of hypofunctioning central cholinergic systems in the observed impairments are discussed. Tianeptine might reduce the inhibiting action of serotonin terminaisons on acetylcholine release and might thus permit normal cholinergic transmission.

Aging↗

[Neurobiology of memory].

This article presents the most significant results and trends concerning current research on the neurobiological basis of memory. The important contribution of neuropsychological research and the resulting constraints that its findings impose to every neurobiological approach are briefly reviewed. The main results about the molecular mechanisms of synaptic plasticity, together with those obtained by several approaches such as electrophysiology, neurochemistry are reported and discussed with respect to their degree of pertinence and coherence with the issues. Finally, the problems relating to the nature, properties, mechanisms of construction and evolution of the internal representations are examined.

Action Potentials↗

Differential involvement of anterior and posterior cingulate cortices in spatial discriminative learning in a T-maze in mice.

The contribution of the anterior and posterior cingulate cortical areas to spatial learning and memory was examined in mice using a behavioral paradigm based on a spatial discrimination task in a T-maze. Multiple injections of small amounts of ibotenic acid were used to produce fiber-sparing lesions of either the anterior (ACC) or the posterior (PCC) cingulate area. Mice with ACC lesions, though learning the initial acquisition and first reversal of the discrimination at about the normal rate, were impaired during the subsequent four reversal sessions. In contrast to control mice, they failed to improve their performance from the first to the last session. Nevertheless, when later required to repeatedly learn the same discrimination over several days (repetitive testing), animals with ACC lesions no longer exhibited any learning deficit. The converse pattern of results was found in mice with PCC lesions. These animals performed much more poorly than control animals during the acquisition and first reversal of the discrimination, but displayed remarkable improvement over the subsequent four reversal sessions, gradually overcoming their initial impairment. However, when later submitted to repetitive testing, these animals again showed a substantial learning deficit. Neither ACC nor PCC cingulate lesions significantly affected the animals' retention capacities as measured by single test-trials over a 24-h interval. Yet, mice with PCC lesions were retarded in reversal learning after a long intersession interval (10 days), indicating that PCC, but not ACC, lesions did interfere with some long-term retention processes. These results imply that the ACC, as a part of the medial frontal cortex, may play a crucial role in temporally ordering a series of spatial responses, whereas the PCC seems to contribute to the formation and retention of each individual spatial response, probably by transmitting information from limbic structures such as the anterior thalamus and hippocampal formation to posterior neocortical association areas.

Adaptation, Psychological↗

Differential effects of chronic ethanol consumptions or thiamine deficiency on spatial working memory in Balb/c mice: a behavioral and neuroanatomical study.

This study was aimed to compare the effects of either a thiamine deficiency or a chronic ethanol consumption on memory and on neuronal density within the median mammillary nucleus. Results showed that alcohol-treated (48 weeks) mice exhibited a behavioral impairment in a sequential alternation task characterized by a progressive decay of alternation rates as a function of the number of trials; such a deficit was not observed in controls and thiamine-deficient subjects. A quantitative analysis using histological sections showed an important reduction of neuronal density within the mammillary bodies following the alcohol treatment but not following thiamine deficiency.

Alcoholism↗

The intermediate stage of sleep in mice.

Seven mice of Balb/C strain were implanted with electrodes to perform sleep-waking recordings. In 100% of the cases, the mice showed, prior to paradoxical sleep, the intermediate stage of sleep characterized by high-amplitude cortical spindles interspersed with slow waves and low-frequency theta rhythm in the dorsal hippocampus. Consequently, the intermediate stage which seems to correspond to a transient functional isolated forebrain does exist in the rat, cat and mouse. in the rat, cat and mouse.

Animals↗

[Analysis of kinetics of consecutive metabolic cerebral activations induced by spatial discrimination testing, using (14C)-glucose, in an eight-arm radial maze in mice].

Regional mapping of relative (14C)-glucose (GLU) uptake was analyzed in Balb/c mice at 3 time intervals (5 min., 1 hr., 3 hrs.) after either the first (Day 1) or the last (Day 9) daily sessions of a spatial discrimination testing procedure in an eight-arm radial maze. On Day 1, increased labelling was found 5 min. post-training in subcortical, hippocampal and cortical regions. Decreased GLU uptake was observed 1 hr. later in the same regions, followed at 3 hrs. post-training by a retarded activation in the above areas and particularly in thalamic and cortical structures. On Day 9, there was only an early (5 min.) post-training increase in metabolic activity followed by a subsequent monotonic decrease over 3 hrs. post-training period.

Animals↗

Age-related changes in the subcortical afferents to the medial frontal cortex in mice: a WGA-HRP study.

The subcortical afferent projections to the mediodorsal part of the frontal cortex were studied both qualitatively and quantitatively in young (3 months), adult (12 months) and aged (22 months) Balb/c mice by means of the retrograde transport of wheat germ agglutinine-horseradish peroxidase (WGA-HRP). A progressive decrease in the number of afferents was observed during aging with a differential pattern of reduction as a function of the subcortical structures. In adult mice a large reduction of afferents occurs in the diagonal band of Broca, the posterior thalamic nucleus, the zona incerta, the lateral hypothalamic area, the nuclei of amygdaloid complex, the posterior hypothalamic nucleus, the reticular pontine nucleus, the dorsal and medial raphe nuclei and the dorsal tegmental nucleus. In aged animals, only the anteromedial and mediodorsal thalamic nuclei, as well as the locus coeruleus appear to be clearly affected.

Aging↗

[Cerebral psychophysiologic study of the processes brought into action by physical context modifications in the short-term recognition of images].

The study of P300 waves and reaction times during the acquisition and recognition of simple symbolic pictures (Signoret's test) shows the extent of "contextual effect" in visual short-term recognition. These results support the "encodage spécifique" theory according to which contextual changes between acquisition and restitution reduce memory efficiency.

Adult↗

Behavioral models of memory and amnesia.

In modelling memory and amnesia, the different forms of cognition must be distinguished. For memory, distinctions between acquisition, storage, and retrieval must be made and the different kinds of memory (e.g., immediate, working, reference) identified. Other notions, such as attention, orientation, and vigilance also belong under the heading "cognition". Thus the term "cognition enhancer" is imprecise because it does not indicate which kind of cognition is to be enhanced. Animal models should be developed for each type of cognition, be based on information from the clinic, and attempt to be specific. Examples of models more specific than the passive avoidance test were discussed and included the radial maze, in which different kinds of memory could be analyzed and correlated with, for example, changes in central cholinergic activity. From the point of view of drug development an important distinction was made between "empirical" and "simulation" models. In other areas of psychopharmacology "empirical" models have been widely used because they show predictable responses to known reference compounds. In the field of cognition there are no generally recognized reference compounds and therefore no "empirical" models. There is therefore a need for "simulation" models which imitate the various aspects of cognition and its pathology. The major criterion for validating this kind of model is that it should show changes similar to those observed in humans either resulting from a particular pathology or from a particular drug treatment.

Amnesia↗

Impairment of memory in a delayed non-matching to place task following mamillary body lesions in mice.

This study assessed the effects of a mamillary body (MM) lesion on memory measured in a delayed non-matching to place task performed in an 8-arm radial maze using BALB/c mice as subjects. In this task, the subjects had to recognize (test-phase) a non-visited arm from a previously visited arm (the sample-place) and were required to enter the non-visited arm in order to get reward. In the first experiment, the difficulty of the recognition was increased by interpolating forced visits (1 to 5; i.e. the study-phase) between the sample-place and the test-phase. In the second experiment, the number of interpolated visits which followed the study-phase was kept constant (5) but the sample-place was placed either before and after the interfering visits. Our results showed that MM subjects were dramatically impaired as compared to controls when required to recognize after 5 but not after 1 interpolated visits (first experiment). However, this deficit was observed only when the sample-place preceded but not when it followed the interpolated visits (second experiment). Our data emphasize the importance of the MM in memory and amnesia.

Animals↗

In vivo modulation of septo-hippocampal cholinergic activity in mice: relationships with spatial reference and working memory performance.

Dopaminergic afferents to the septum mediate a tonic and trans-synaptic inhibitory control on the cholinergic neurones of the septo-hippocampal pathway. Lesion of these afferents using 6-hydroxydopamine (6-OHDA) results in a chronic and specific increase of hippocampal cholinergic activity in mice. The consequence of this in vivo modulation of hippocampal cholinergic activity on the acquisition of both a spatial discrimination and a working memory (delayed non-matching to place) task in an 8-arm radial maze by C57BL/6 mice were investigated. Combined neurochemical and behavioural analyses revealed significant correlations between hippocampal sodium-dependent high-affinity choline uptake activation induced by testing and performance measures. In the first experiment 6-OHDA-treated mice compared to control and vehicle-injected mice showed a transient (day 2) but significant facilitation of their spatial discrimination performance which appears to be better related to the working but not to the reference memory component of the task. This hypothesis is strengthened by the results of the second experiment which shows an amelioration of working memory performance when the septo-hippocampal cholinergic pathway is specifically activated in vivo.

Afferent Pathways↗

Modifications in number and morphology of dendritic spines resulting from chronic ethanol consumption and withdrawal: a Golgi study in the mouse anterior and posterior hippocampus.

Using Golgi-impregnated mice brains, the effects of 2.5, 6.5, and 9.5 months of chronic ethanol consumption were investigated with regard to morphology and number of dendritic spines of CA1 hippocampal pyramidal neurons. The posterior part of the hippocampus was more sensitive to the effects of ethanol consumption than the anterior one. In the posterior part of the structure, the number of dendritic spines was reduced by 25 and 33% after 6.5 and 9.5 months of treatment, respectively, as compared to age-matched controls. Moreover, the remaining spines appeared shorter than normal. After 9 months of ethanol treatment followed by 0.5, 1, and 2 months of withdrawal, the number of dendritic spines was reduced by 24, 19, and 7.5% in the posterior hippocampus, respectively. In the anterior part of the hippocampus, a significant loss of dendritic spines (-20.5%) was observed only after 9.5 months of ethanol consumption. After 1 month of withdrawal, both number and morphology of dendritic spines appeared normal in the anterior hippocampus. These results demonstrate that chronic alcohol consumption leads to morphological alterations and loss of dendritic spines in the hippocampus. However, both dendritic spine number and morphology progressively return to normal values after 2 months of withdrawal. This phenomenon is another example of neuronal plasticity in adult animal brain.

Alcoholism↗

Intertrial interval dependent effect of lateral hypothalamic stimulation on spontaneous alternation behavior in a T-maze.

Spontaneous alternation behavior in a T-maze was studied in mice of the BALB/c strain implanted with a stimulation electrode in the lateral hypothalamus (LH). For animals receiving no electrical stimulation spontaneous alternation rates decreased as a function of the increasing time interval between the first and the second trial (intertrial interval ITI). Thus, as compared to chance rate alternation (41.4%), mice significantly alternated at the 30 sec ITI (73.2%), exhibited a slight but not significant tendency to alternate at 30 min (51.8%) and performed very close to chance at 6 hr (39.3%). Stimulation of the LH, using a low current intensity (5 microA) during the first arm-choice, modifies subsequent arm-choice tested on the second trial. The direction of the effect, however, is highly dependent on the ITI. Thus, as compared to nonstimulated animals, stimulated mice show a strong preference to return to the previously visited arm when the ITI was 30 min, while for an ITI of 6 hr they, in fact, significantly avoid that arm (alternation). These results indicate that LH stimulation induces facilitative effects on memory for events occurring on the 1st trial as clearly shown for the 6 hr ITI. In addition to its general facilitative effect, stimulation could induce a place-reward association of short-duration which could explain the fact that animals tend to return to the same arm at 30 min. Alternatively, it is suggested that stimulation might have short-lasting amnesiant properties. Both of these hypotheses are discussed.

Animals↗

Septal alpha-noradrenergic antagonism in vivo blocks the testing-induced activation of septo-hippocampal cholinergic neurones and produces a concomitant deficit in working memory performance of mice.

In order to test the hypothesis that alpha-noradrenergic receptors in the septum 1) play an important functional role in the mediation of trans-synaptic control of the neurones of the cholinergic septo-hippocampal pathway and 2) produce resultant modulation of working memory performance, we have investigated the effects in vivo of the acute intraseptal injection of an alpha-antagonist, phenoxybenzamine, in mice. Neurochemical analysis was performed using measures of the kinetics of sodium-dependent high-affinity choline uptake in samples of hippocampus from injected mice and their relevant controls in both quiet conditions and immediately following selective working memory testing in an 8-arm radial maze. Results show that whereas the injection of phenoxybenzamine produces no significant alteration of the activity of the cholinergic septo-hippocampal neurones in quiet conditions, the pretrial (20 min) administration of this drug almost totally abolished the usually observed increase in hippocampal cholinergic activity induced by testing. This inhibition of cholinergic activation was associated with a parallel working memory deficit. The results provide further direct support for the hypothesis that septal noradrenergic afferents via alpha-receptors mediate a phasic and net excitatory trans-synaptic influence on the cholinergic septo-hippocampal pathway during working memory testing and thereby significantly contribute to the modulation of the level of working memory performance.

Action Potentials↗