A Marighetto

Publications (19)51.59 Total impact

• Article: Functions for adult neurogenesis in memory: an introduction to the neurocomputational approach and to its contribution.

  X Noguès, M M Corsini, A Marighetto, D N Abrous
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  ABSTRACT: Until recently, it was believed that the introduction of new neurons in neuronal networks was incompatible with memory function. Since the rediscovery of adult hippocampal neurogenesis, behavioral data demonstrate that adult neurogenesis is required for memory processing. We examine neurocomputational studies to identify which basic mechanisms involved in memory might be mediated by adult neurogenesis. Mainly, adult neurogenesis might be involved in the reduction of catastrophic interference and in a time-related pattern separation function. Artificial neuronal networks suggest that the selective recruitment of new-born or old neurons is not stochastic, but depends on environmental requirements. This leads us to propose the novel concept of "soft-supervision". Soft-supervision would be a biologically plausible process, by which the environment is able to influence activation and learning rules of neurons differentially.
  Behavioural brain research 08/2011; 227(2):418-25. · 3.22 Impact Factor
• Article: Comparative effects of the alpha7 nicotinic partial agonist, S 24795, and the cholinesterase inhibitor, donepezil, against aging-related deficits in declarative and working memory in mice.

  A Marighetto, S Valerio, A Desmedt, J N Philippin, C Trocmé-Thibierge, P Morain
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  ABSTRACT: The comparative effects of a newly described specific alpha7 nAChR partial agonist, S 24795, and a cholinesterase inhibitor, donepezil, currently used as a symptomatic Alzheimer's disease treatment were studied in two mouse models of aging-related memory deficits. We employed radial arm-maze paradigms assessing short-term working memory (STWM, experiment A) and mnemonic flexibility, a cardinal property of long-term declarative (LTDM, experiment B). Both compounds were administered daily at 0.3 and 1 mg/kg subcutaneously (~3 weeks). In the STWM experiment, vehicle-treated aged mice displayed a severe and persistent deficit in the retention of successive arm visits in comparison to younger controls. S 24795 at 1 mg/kg (trends at 0.3 mg/kg) and donepezil at 0.3 mg/kg (but not 1 mg/kg) exerted beneficial effects on this deficit: The performance of aged mice treated with these drugs remarkably increased across the testing days and almost reached young adult performance level. In the critical test trials of memory flexibility (i.e., LTDM), in experiment B, S 24795 at 1 mg/kg (trends at 0.3 mg/kg) and donepezil at the dose of 1 mg/kg (but not 0.3 mg/kg) improved aged mice performance. This preclinical demonstration that S 24795 restored specific age-related memory deficits with as much efficacy as donepezil adds to recent literature in highlighting the potential interest of an alpha7 nAChR drug as a symptomatic AD therapeutic.
  Psychopharmacologia 05/2008; 197(3):499-508. · 4.08 Impact Factor
• Article: Alleviation of a selective age-related relational memory deficit in mice by pharmacologically induced normalization of brain retinoid signaling.

  N Etchamendy, V Enderlin, A Marighetto, R M Vouimba, V Pallet, R Jaffard, P Higueret
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  ABSTRACT: Vitamin A and its derivatives, the retinoids, have been implicated recently in the synaptic plasticity of the hippocampus and might therefore play a role in associated cognitive functions. Acting via transcription factors, retinoids can regulate gene expression via their nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors]. In a series of experiments, the present study investigated the possible role of age-related downregulation of retinoid-mediated transcription events in the cognitive decline seen in aged mice. We observed that the brain (and hippocampal) levels of retinoid receptors and the expression of specific associated target genes were restored to presenescent (adult) levels in aged mice after acute administration (150 microg/kg, s.c.) of retinoic acid (RA). These effects of RA, however, could be abolished by the coadministration of an RAR antagonist. RA was also demonstrated to alleviate the age-related deficit in the CA1 long-term potentiation efficacy of aged mice in vivo. Moreover, RA was found to alleviate completely the performance deficit of aged mice to the control level in a two-stage spatial discrimination paradigm designed to assess relational memory. This promnesic effect of RA was again susceptible to abolition by RAR antagonist treatment. The parallel molecular, cellular, and behavioral correlates associated with the decrease of retinoid receptor expression and its normalization demonstrated here suggest that the fine regulation of retinoid-mediated gene expression is fundamentally important to optimal brain functioning and higher cognition. Specifically, a naturally occurring dysregulation of retinoid-mediated molecular events might be a potential etiological factor for cognitive deterioration during senescence.
  Journal of Neuroscience 09/2001; 21(16):6423-9. · 7.11 Impact Factor
• Article: Knowing which and knowing what: a potential mouse model for age-related human declarative memory decline.

  A Marighetto, N Etchamendy, K Touzani, C C Torrea, B K Yee, J N Rawlins, R Jaffard
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  ABSTRACT: The present study was built on the original report of Eichenbaum et al. [Eichenbaum, H., Fagan, A., Mathews, P. & Cohen, N.J. (1988), Behav. Neurosci., 102, 3531-3542] on the contrasting effects of fornix lesion in different versions of an odour-guided discrimination task in rats, and attempted to extend this into a mouse model for the preferential loss of declarative memory seen in human senescence. Each of the two experiments reported here consisted of a two-stage paradigm, with an initial learning phase followed by a test phase. The information acquired in the first stage was identical in both experiments, i.e. the valence or reward contingency associated with six (three positive and three negative) arms of a radial maze. The only parameter which was varied between Experiment A and B, and also between the two successive stages within each experiment, was the way of presenting the arms to the mice, i.e. either in pairs (simultaneous discriminations) or one at a time (successive go : no-go discrimination). Performance in the first stage demonstrated that our aged mice were impaired in learning concurrent simultaneous discriminations but not successive go/no-go discrimination, thereby resembling that reported in rats with hippocampal damage. Most importantly, our present set of data supports the conclusion that two forms of memory expression for the same piece of acquired experience can be assessed in the same subjects by manipulating the way of presenting two arms that were previously experienced separately. These two forms of memory expressions are differentially affected in aged mice, thereby demonstrating the highly selective and specific deleterious effect of ageing.
  European Journal of Neuroscience 10/1999; 11(9):3312-22. · 3.63 Impact Factor
• Article: The effects of cytotoxic entorhinal lesions and electrolytic medial septal lesions on the acquisition and retention of a spatial working memory task.

  A Marighetto, B K Yee, J N Rawlins
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  ABSTRACT: Rats with lesions either of medial septal nucleus (MSN) or the entorhinal cortex (ECx) were compared postoperatively with unoperated controls in a discrete-trial, delayed matching-to-position (DMTP) task, conducted on an elevated T-maze. A DMTP trial consisted of two consecutive visits to the maze: an information run and a choice run. The animals were first forced to visit a randomly selected choice arm in the information run. In the choice run, the correct response was to match the choice arm that had been visited on the information run, regardless of whether the information run itself had been rewarded or not. MSN animals failed to succeed in this task, performing at close to chance level throughout training. On the other hand, ECx rats consistently perform at a level comparable with that of unoperated controls; both groups attained more than 90% correct after 192 trials. Long-term retention testing was carried out after an intermission of 4 weeks, when the same task was re-administered to the ECx and unoperated control animals. ECx animals showed significantly less saving than controls in the retention test. In contrast, when the retention interval within a DMTP trial was increased by the imposition of a 20-s delay between the information and choice runs, the ECx group was not selectively affected by this manipulation.
  Experimental Brain Research 05/1998; 119(4):517-28. · 2.39 Impact Factor
• Article: Cytosolic hippocampal PKC and aging: correlation with discrimination performance.

  A Pascale, X Noguès, A Marighetto, J Micheau, F Battaini, S Govoni, R Jaffard
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  ABSTRACT: Adult and aged mice were submitted to a discrimination task in a radial maze (regular trials), and then to probe trials requiring them to form relational representations. Three weeks later, animals were again tested for regular and probe trials. Following another interval of 3 weeks, individual hippocampal cytosolic calcium-dependent and -independent PKC activities were measured. Performance of aged animals was impaired on probe but not regular trials and aged mice had lower hippocampal cytosolic calcium-dependent and -independent PKC activities than adults. Performance on probe trials was specifically correlated with calcium-dependent PKC activity. This suggests a specific relationship between the ability to form relational representations and hippocampal cytosolic calcium-dependent PKC activity.
  Neuroreport 04/1998; 9(4):725-9. · 1.66 Impact Factor
• Article: Long-term potentiation and long-term depression in the lateral septum in spatial working and reference memory.

  R Jaffard, R M Vouimba, A Marighetto, R Garcia
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  ABSTRACT: We report two experiments conducted on a radial arm maze in the mouse showing that training could either enhance or reduce the efficacy of the fimbria-lateral septal synapses. It is suggested that the direction of change is determined by the kind of situation the animal is faced with (ie trial-dependent, respectively).
  Journal of Physiology-Paris 02/1996; 90(5-6):339-41. · 1.31 Impact Factor
• Article: Effects of intraseptally injected glutamatergic drugs on hippocampal sodium-dependent high-affinity choline uptake in "naive" and "trained" mice.

  A Marighetto, J Micheau, R Jaffard
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  ABSTRACT: We have previously reported that spatial reference memory (RM) training-induced alterations in hippocampal cholinergic activity as measured by sodium-dependent high-affinity choline uptake (SDHACU). Each training session was found to induce an immediate (30 s) increase in SDHACU followed (30 s to 15 min posttest) by a deactivation and long-lasting inhibition (15 min to 24 h) of this cholinergic marker. The present experiments were designed to assess the role of septal glutamatergic receptors in this posttraining cholinergic deactivation. In the first experiment, the effects of intraseptal injections of different doses of glutamic acid and glutamatergic antagonists (kynurenic acid, KYN, and AP5) on hippocampal SDHACU were studied in awake but otherwise resting (i.e., naive) mice. The results showed that glutamic acid at the lowest dose used (5 ng) produced a decrease in SDHACU, whereas both glutamatergic antagonists produced a dose-related increase in this cholinergic marker. It was concluded that septal glutamatergic receptors mediate a tonic inhibitory input on the cholinergic cells. Hence, in a second experiment the effect of intraseptal injections of KYN (5 ng) on the training-induced changes in hippocampal cholinergic activity were assessed following variable amounts of radial maze RM training. Trained mice were injected 20 min before the first or the ninth training session and killed 30 s or 15 min posttraining for determination of SDHACU. KYN slowed the posttesting cholinergic deactivation (disinhibition), this effect being more marked in good learners than in bad learners. The present findings suggest that septal glutamatergic receptors mediate an inhibitory input on the cholinergic cells, and that this input could play a role in memory consolidation.
  Pharmacology Biochemistry and Behavior 12/1994; 49(3):689-99. · 2.53 Impact Factor
• Article: Effects of intraseptally injected noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake in 'resting' and 'trained' mice.

  A Marighetto, R Jaffard, J Micheau
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  ABSTRACT: It has been shown in numerous studies that memory testing can alter presynaptic cholinergic activity within the hippocampus. In the present experiments, the role of the noradrenergic input to the septal cholinergic neurons in the immediate increase in cholinergic activity induced by the first training session of a spatial reference memory task in an 8-arm radial maze was investigated. The effects of bilateral intraseptal injections of noradrenergic drugs on hippocampal sodium-dependent-high-affinity-choline-uptake (SDHACU) were studied in 'resting' animals (basal level) or in 'trained' animals injected 20 min before training and sacrificed immediately after the test. The results showed that: (1) the injection of maprotiline, a noradrenaline reuptake inhibitor (0.06 ng/site), induced an increase in hippocampal SDHACU in 'resting' animals, whereas the alpha 2-adrenoceptor agonist UK 14304 (1.5 ng) significantly reduced the basal level of SDHACU; (2) none of the alpha-adrenoceptor antagonists used (phenoxybenzamine, 10 and 100 ng; BE 2254, 100 and 500 ng; yohimbine, 0.5 and 50 ng) significantly affected the basal level of hippocampal SDHACU, and only the alpha 1-adrenoceptor antagonist BE 2254 (500 ng) significantly reduced the testing-induced activation of SDHACU. Taken together, these findings suggest that noradrenaline may exert a bimodal regulatory influence on the activity of septo-hippocampal cholinergic neurons. The behavior-induced activation of hippocampal SDHACU could be partly mediated by the stimulation of alpha 1-adrenoceptors, whereas postsynaptic alpha 2-adrenoceptors may be important for the maintenance of a tonic inhibition of the steady-state cholinergic activity in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
  Brain Research 08/1994; 652(1):120-8. · 2.73 Impact Factor
• Article: Relationships between testing-induced alterations of hippocampal cholinergic activity and memory performance on two spatial tasks in mice.

  A Marighetto, J Micheau, R Jaffard
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  ABSTRACT: Alterations in hippocampal cholinergic activity associated with different types and/or stages of learning were explored using measures of sodium-dependent high-affinity choline uptake (SDHACU) in the hippocampus of C57BL/6 mice. Animals were divided into 'active' subjects submitted to memory testing before being killed and 'quite' controls. 'Active' subjects were trained in a radial-arm maze on either a discrimination task (mixed Working Memory (WM)-Reference Memory (RM) task) or a Delayed-Non-Matching-To-Place task (more selective WM-task). In the discrimination task mice were sacrificed after either the 1st, 2nd, 3rd or 9th daily session of training and at intervals of either 30 s, 15 min, 24 h or 9 days post-test. In the DNMTP-task all subjects of the 'active' groups were sacrificed after 12 days of training at either 30 s or 24 h post-test. Results showed that: (1) Both types of training induced an immediate (30 s post-test) increase of hippocampal SDHACU as compared to 'quite' control condition. (2) In the discrimination task, this immediate increase in SDHACU was followed by a decrease leading to a long-lasting (24 h and 9 days) inhibition of this cholinergic marker. This secondary decrease in SDHACU occurred earlier (15 min post-test) at the end (9th session) than at the beginning (1st-3rd sessions) of training. Thus, as training progressed there was a shortening of the testing-induced cholinergic activation. (3) By contrast, in the DNMTP-task, SDHACU was still increased at the interval of 24 h following the last session of DNMTP-training. (4) The amplitudes of both the immediate (30 s) increase and subsequent secondary (15 min) decrease in SDHACU after the last (9th) session of discrimination training were significantly related to the rate of acquisition and behavioural profile for individual animals. Subjects that had displayed better response accuracy across the 9 days of training exhibited the highest SDHACU at 30 s post-test and the lowest at 15 min post-test. These results are discussed in the context both of previous findings on the effects of training on cholinergic activity, and of contemporary models of hippocampal function. It is suggested that (1) an increase in hippocampal cholinergic transmission during testing would facilitate the acquisition of a 'relational' kind of informations (spatial WM and RM); (2) the post-training consolidation (spatial RM) of information would be facilitated by a decrease and long-lasting inhibition of hippocampal cholinergic activity.
  Behavioural Brain Research 10/1993; 56(2):133-44. · 3.42 Impact Factor
• Article: Effects of tianeptine on spontaneous alternation, simple and concurrent spatial discrimination learning and on alcohol-induced alternation deficits in mice.

  R. Jaffard, E. Mocaer, J-C. Poignant, J. Micheau, A. Marighetto, M. Meunier, D. Béracochéa
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  ABSTRACT: The effects of systemic administration of tianeptine, a new psychotropic agent with antidepressant properties, were investigated on spontaneous alternation behavior, and on simple and concurrent spatial discrimination, in normal mice of the BALB/c strain. Tianeptine increased rates of spontaneous T-maze alternation, facilitated retention of a T-maze left-right discrimination, and speeded up acquisition of concurrent discrimination in a radial maze. These effects were consistent across successive experiments with a dose of 10mg/kg; lower doses (2.5 and 5.0mg/kg) had less or no effect depending on the task. These results, together with theoretical considerations, led us to investigate the effect of tianeptine on the sequential-specific alternation deficit induced by long-term ethanol administration in the same strain of mice. Results showed that, at the dose of 10mg/kg, the drug completely alleviated the alcohol-induced deficit. Unlike tianeptine, fluoxetine impaired discrimination performance in the radial maze. These data are discussed in light of the effects of tianeptine on serotonergic transmission and of the role of serotonin and acetylcholine in learning and memory processes.
  Behavioural pharmacology 03/1991; 2(1):37-46. · 2.85 Impact Factor
• Article: 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.

  A Marighetto, T Durkin, A Toumane, C Lebrun, R Jaffard
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  ABSTRACT: 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.
  Pharmacology Biochemistry and Behavior 12/1989; 34(3):553-8. · 2.53 Impact Factor
• Article: The durations of hippocampal and cortical cholinergic activation induced by spatial discrimination testing of mice in an eight-arm radial maze decrease as a function of acquisition.

  A Toumane, T Durkin, A Marighetto, R Jaffard
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  ABSTRACT: Sodium-dependent high-affinity choline uptake velocities in P2 fractions of the hippocampus and cortex of mice were analyzed at different times following both the first (Day 1) and last (Day 9) daily sessions of a spatial discrimination testing procedure in an eight-arm radial maze. Results showed that the immediate (30 s) post-training increase in mean hippocampal and cortical cholinergic activity observed on Day 1 did not significantly vary over days despite a marked and progressive improvement of discrimination performance. In contrast, the duration of these activations was considerably shortened in both structures between Days 1 (more than 1 hr) and 9 (about 15 min). The possible involvement of these changes in memory consolidation processes is discussed.
  Behavioral and Neural Biology 10/1989; 52(2):279-84.
• Article: Experimental dissociation of memory systems in mice: behavioral and neurochemical aspects.

  R Jaffard, T Durkin, A Toumane, A Marighetto, C Lebrun
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  ABSTRACT: Evidence for different types of memory in mice may lead to development of animal models for human memory disorders and provides informations on neurobiological systems underlying these processes. Series of experiments in mice, using a 8-arm radial maze with or without cholinergic drugs or chronic alcohol consumption supply arguments for multiple memory stores and for cholinergic influence greatest for short-term system. Studies of differential cholinergic activation following training militate for dissociation in time of hippocampal and cortical cholinergic pathways. Age-related memory involvement seems to be associated with an attenuation of central cholinergic activation. Several problems inherent to sensitivity and selectivity of the tasks remain in discussion.
  Archives of gerontology and geriatrics. Supplement 02/1989; 1:55-70.
• Article: Differential hippocampal and cortical cholinergic activation during the acquisition, retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze by mice.

  A Toumane, T Durkin, A Marighetto, D Galey, R Jaffard
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  ABSTRACT: Possible differentiation of the intervention of cholinergic septohippocampal and magnocellular forebrain (NBM) projections to cortex during learning and memory processes has been investigated directly using mice. High-affinity choline uptake velocities in the hippocampus and cortex were analyzed, in parallel, at various periods during the acquisition, over 8 days, as were the subsequent retention, reversal and extinction of a spatial discrimination in an 8-arm radial maze. Initial acquisition induced an immediate (30 s) and long-lasting (approx. 3 h) increase in mean hippocampal (+33%) and cortical (+23%) cholinergic activities. The time course of this activation was structure-dependent and correlations of hippocampal-cortical cholinergic activities showed large and consistent alterations as a function of time after training. Cholinergic activation in both brain regions was observed immediately following each daily training session with amplitudes which did not vary significantly in spite of a progressive daily increment in performance. Following acquisition mice were tested for retention, reversal and extinction: 30 s following the retention session, cholinergic activation was observed in both cortex and hippocampus, with magnitudes similar to those observed at the end of acquisition. However, in the reversal and extinction groups, a treatment-dependent attenuation of cholinergic activation was observed which was accompanied by a significant loss of correlation of cholinergic activity between these two brain regions. The results are discussed in relation to the concepts of reference and working memory and also to novelty, stress, arousal and frustrative non-reward. The data constitute direct experimental evidence for a differential involvement of cholinergic septohippocampal and NBM-cortical projections in learning and memory processes.
  Behavioural Brain Research 11/1988; 30(3):225-34. · 3.42 Impact Factor
• Article: [An animal model of human declarative (relational) memory and of its dysfunction].

  R Jaffard, N Etchamendy, A Desmedt, A Krazem, C Cortes-Torrea, A Marighetto
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  ABSTRACT: The present work was aimed at determining, both at the psychological and at the neurobiological levels, aspects of rodent memory that fall into line with human declarative memory which is known to be selectively impaired in amnesic subjects and during the course of ageing. The ability to compare and to contrast items in memory, and to support inferential use of memories in novel situations (flexibility), were considered to be the two key psychological features of human declarative memory that were altered by both hippocampal lesions and hippocampal dysfunction. Adult and aged mice were trained on learning tasks using two-stage paradigms, the aim of which was to assess memory performance through these two psychological aspects in the same subjects. Results suggest that ageing specifically impairs the ability to both compare and contrast items in memory (declarative/relational memory based on complex associations), without altering memory based on simple S-R associations (procedural memory). Hippocampal lesions in adult mice produced the same dissociation between relational memory (impaired) and procedural memory (spared). Pharmacological experiments showed that, depending on the drug used, the relational memory deficit of aged mice may be selectively reversed (i.e. without changes in procedural memory) and that the behavioural efficacy of certain treatments was shown to parallel their potency in re-establishing normal (i.e. adult) levels of hippocampal plasticity-related mechanisms. Together with previous findings, these results suggest that the storage and use of relational representations would critically depend on the plasticity of hippocampal synapses, which via their connections with cortical areas, would support the storage of associations between perceptual, behavioral and cognitive events.
  Thérapie 55(4):477-85. · 0.30 Impact Factor
• Article: A comparison of the working memory performances of young and aged mice combined with parallel measures of testing and drug-induced activations of septo-hippocampal and nbm-cortical cholinergic neurones.

  C Lebrun, T P Durkin, A Marighetto, R Jaffard
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  ABSTRACT: The spatial working memory performances of young (2 months) and aged (24-26 months) mice of the C57BL/6 strain were compared using a delayed nonmatching to place (DNMTP) protocol in an automated 8-arm radial maze. The aged mice were observed to exhibit a selective and interference-related memory deficit. Parallel neurochemical analysis of the activity of septo-hippocampal and nbm-cortical cholinergic neurones in vivo was conducted using measures of sodium-dependent high-affinity choline uptake. Results showed that whereas the level of cholinergic activity in both brain regions varied less than 10% between young and aged mice in quiet conditions (basal) the activation usually observed at 30-sec posttest (+20-25%) in young mice was greatly attenuated in the frontal cortex and almost totally absent in the hippocampus of aged mice. In view of these results a complementary experiment was carried out in order to test the intrinsic ability of septo-hippocampal cholinergic neurones to activate using acute injection of scopolamine (1 mg/kg IP 20 min) to both young and aged mice in quiet conditions. The drug injection resulted in a very large (+70%) increase in hippocampal high-affinity choline uptake and with amplitudes which did not vary significantly between young and aged subjects. These observations attest to a relatively well-preserved state of central cholinergic neurones and an intact capacity to activate normally when challenged pharmacologically in aged mice. The results strongly suggest that the loss of cholinergic activation and associated memory deficit in aged mice might rather be related to a hypofunction of phasically active transsynaptic processes which normally mediate the activation of these cholinergic pathways during memory testing.
  Neurobiology of Aging 11(5):515-21. · 6.19 Impact Factor
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  Available from: Robert J Jaffard

  Article: Further evidence for a dissociation between different forms of mnemonic expressions in a mouse model of age-related cognitive decline: effects of tacrine and S 17092, a novel prolyl endopeptidase inhibitor.

  A Marighetto, K Touzani, N Etchamendy, C C Torrea, G De Nanteuil, D Guez, R Jaffard, P Morain
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  ABSTRACT: It has been demonstrated previously on the radial maze that the emergence of an age-related mnemonic impairment is critically dependent on the form which the discrimination problems took. Hence, when the arms were presented one by one (i.e., successive go-no-go discrimination), both adult and aged mice learned to distinguish between positive (baited) and negative (unbaited) arms readily, as evidenced by their increased readiness to enter positive relative to negative arms (i.e., by a differential in arm-entry latencies). A selective impairment in the aged mice was seen when these arms were presented subsequently as pairs, such that the mice were confronted with an explicit choice (i.e., simultaneous 2-choice discrimination). When discriminative performance was measured by the differential run speed between positive and negative arms, aged mice were also impaired. This was particularly pronounced in the 2-choice discrimination condition. We examined the effects of tacrine (3mg/kg, subcutaneously) or S 17092 (10mg/kg, orally) in aged mice on the three behavioral indices of this 2-stage spatial discrimination paradigm. The results indicated that: (1) Tacrine, but not S 17092, enhanced the acquisition of go-no-go discrimination as reflected in arm-entry latencies; (2) both drugs improved choice accuracy in simultaneous discrimination, although the effect of tacrine was less striking and, in particular, far from statistical significance in the very first 2-choice responses; and (3) neither drugs significantly affected run-speed performance. We conclude further that the specific patterns of drug effects on the three indices of discriminative performance might suggest that each index is associated with a distinct form of mnemonic expression relying on separate neural systems.
  Learning &amp Memory 7(3):159-69. · 4.22 Impact Factor
• Article: Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians.

  J.P. Bourdineaud, N Bellance, G. Bénard, D. Brèthes, M. Fujimura, P Gonzalez, A Marighetto, R. Maury-Brachet, C. Mormède, V. Pedron, J N Philippin, R Rossignol, W. Rostene, M. Sawada, M. Laclau
  Environmental health : a global access science source [electronic resource].