Aline Marighetto

Aline Marighetto
French Institute of Health and Medical Research | Inserm · Neurocentre Magendie U862

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79
Publications
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Publications

Publications (79)
Article
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Context Impaired cognition and altered quality of life (QoL) may persist despite long-term remission of Cushing’s disease (CD). Persistent comorbidities and treatment modalities may account for cognitive impairments. Therefore, the role of hypercortisolism per se on cognitive sequelae remains debatable. Objective To investigate whether memory and...
Article
One of the cardinal features of post-traumatic stress disorder (PTSD) is a paradoxical memory alteration including both emotional hypermnesia for salient trauma-related cues and amnesia for the surrounding traumatic context. Interestingly, some clinical studies have suggested that contextual amnesia would causally contribute to the PTSD-related hyp...
Article
Full-text available
Moderate stress increases memory and facilitates adaptation. In contrast, intense stress can induce pathological memories as observed in post-traumatic stress disorders (PTSD). A shift in the balance between the expression of tPA and PAI-1 proteins is responsible for this transition. In conditions of moderate stress, glucocorticoid hormones increas...
Preprint
Full-text available
The predisposition of Autism Spectrum Disorder (ASD) to Post-Traumatic Stress Disorder (PTSD) remained to be established. Here, we show that exposure to a single mild stressful event induces maladaptive memory, and recapitulates features of PTSD, which is associated with the broad dysfunction of the prefrontal-hippocampo-amygdalar network. Using op...
Article
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GluN2B subunits of NMDA receptors have been proposed as a target for treating age‐related memory decline. They are indeed considered as crucial for hippocampal synaptic plasticity and hippocampus‐dependent memory formation, which are both altered in aging. Because a synaptic enrichment in GluN2B is associated with hippocampal LTP in vitro, a simila...
Article
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Injection of corticosterone (CORT) in the dorsal hippocampus (DH) can mimic post-traumatic stress disorder (PTSD)—related memory in mice: both maladaptive hypermnesia for a salient but irrelevant simple cue and amnesia for the traumatic context. However, accumulated evidence indicates a functional dissociation within the hippocampus such that conte...
Article
Full-text available
Post-traumatic stress disorder (PTSD) is characterized by emotional hypermnesia on which preclinical studies focus so far. While this hypermnesia relates to salient traumatic cues, partial amnesia for the traumatic context can also be observed. Here, we show in mice that contextual amnesia is causally involved in PTSD-like memory formation, and tha...
Article
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The organization of spatial information, including pattern completion and pattern separation processes, relies on the hippocampal circuits, yet the molecular and cellular mechanisms underlying these two processes are elusive. Here, we find that loss of Vangl2, a core PCP gene, results in opposite effects on pattern completion and pattern separation...
Article
Declarative memory formation depends on the hippocampus and declines in aging. Two functions of the hippocampus, temporal binding and relational organization (Rawlins and Tsaltas, 1983; Eichenbaum et al., 1992; Cohen et al., 1997), are known to decline in aging (Leal and Yassa, 2015). However, in the literature distinct procedures have been used to...
Article
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Positive allosteric modulators of AMPA receptors (AMPA-PAMs) are described to facilitate cognitive processes in different memory-based models. Among them, S 47445 is a novel potent and selective AMPA-PAM. In order to assess its efficacy after repeated administration, S 47445 effect was evaluated in two aging-induced memory dysfunction tasks in old...
Article
Full-text available
Temporal binding, the process that enables association between discontiguous stimuli in memory, and relational organization, a process that enables the flexibility of declarative memories, are both hippocampus-dependent and decline in aging. However, how these two processes are related in supporting declarative memory formation and how they are com...
Article
17β-Estradiol (17β-E2) is a steroid with pleiotropic actions. In addition to being a sexual hormone, it is also produced in the brain where it modulates the reproductive axis. It has been shown that 17β-E2 also acts on synaptic plasticity and plays a role in neurological pathways and in neurodegenerative diseases. Assaying this steroid in the brain...
Article
The function of cortical GABAergic interneurons is largely determined by their integration into specific neural circuits, but the mechanisms controlling the wiring of these cells remain largely unknown. This is particularly true for a major population of basket cells that express the neuropeptide cholecystokinin (CCK). Here we found that the tyrosi...
Article
Full-text available
A distinction has always been made between long-term and short-term memory (also now called working memory, WM). The obvious difference between these two kinds of memory concerns the duration of information storage: information is supposedly transiently stored in WM while it is considered durably consolidated into long-term memory. It is well ackno...
Data
Recapitulative behavioral results. Results are expressed as a mean percentage of correct choices, SEM and number of animals for each training group (LIWM, HIWM, mLIWM, mHIWM, LIWM90 and HIWM90) and for each block of two sessions (or trial) in experiments 1, 2 and 3. (PDF)
Article
Full-text available
For centuries philosophical and clinical studies have emphasized a fundamental dichotomy between emotion and cognition, as, for instance, between behavioral/emotional memory and explicit/representative memory. However, the last few decades cognitive neuroscience have highlighted data indicating that emotion and cognition, as well as their underlyin...
Article
Identifying the underlying cellular mechanisms of episodic memory is an important challenge, since this memory, based on temporal and contextual associations among events, undergoes preferential degradation in aging and various neuropsychiatric disorders. Memory storage of temporal and contextual associations is known to rely on hippocampal N-methy...
Article
For over a century clinicians have consistently described the paradoxical co-existence in posttraumatic stress disorder (PTSD) of sensory intrusive hypermnesia and declarative amnesia for the same traumatic event. Although this amnesia is considered as a critical aetiological factor of the development and/or persistence of PTSD, most current animal...
Article
Full-text available
The neuroimaging literature has shown consistent decreases in fMRI activity in the hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the hippocampus and caudate nucleus respectively. Therefore, since the proportion of people using spati...
Article
The neuroimaging literature has shown consistent decreases in functional magnetic resonance imaging (fMRI) activity in the hippocampus of healthy older adults engaged in a navigation task. However, navigation in a virtual maze relies on spatial or response strategies known to depend on the hippocampus and caudate nucleus, respectively. Therefore, s...
Article
Full-text available
Methylmercury (MeHg) is a potent neurotoxin, and human beings are mainly exposed to this pollutant through fish consumption. We addressed the question of whether a diet mimicking the fish consumption of Wayanas Amerindians from French Guiana could result in observable adverse effects in mice. Wayanas adult men are subjected to a mean mercurial dose...
Article
Increased consumption of high-fat diet (HFD) leads to obesity and adverse neurocognitive outcomes. Childhood and adolescence are important periods of brain maturation shaping cognitive function. These periods could consequently be particularly sensitive to the detrimental effects of HFD intake. In mice, juvenile and adulthood consumption of HFD ind...
Article
A radial maze concurrent spatial discrimination learning paradigm consisting of two stages was previously designed to assess the flexibility property of relational memory in mice, as a model of human declarative memory. Aged mice and young adult mice with damage to the hippocampus, learned accurately Stage 1 of the task which required them to learn...
Article
Full-text available
Posttraumatic stress disorder (PTSD) is characterized by a hypermnesia of the trauma and by a memory impairment that decreases the ability to restrict fear to the appropriate context. Infusion of glucocorticoids in the hippocampus after fear conditioning induces PTSD-like memory impairments and an altered pattern of neural activation in the hippoca...
Article
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 invo...
Article
In the present chapter, we describe our own attempts to improve our understanding of the pathophysiology of memory in aging. First, we tried to improve animal models of memory degradations occurring in aging, and develop common behavioral tools between mice and humans. Second, we began to use these behavioral tools to identify the molecular/intrace...
Article
Even though "procholinergic" drugs are almost the sole kind of treatments currently used as cognitive enhancers in patients with Alzheimer's disease, the role of acetylcholine (ACh) in learning and memory is still poorly understood. In this short review, we focus on the septo-hippocampal cholinergic system and try to demonstrate that understanding...
Article
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Isoflavones are naturally occurring molecules present in significant amount in many leguminous, some of which are edible plants. Isoflavones exhibit similarities in their chemical structure with steroidal estrogens. This allows them to trigger some of the endogenous physiocellular signalization processes of estrogens that are known to occur natural...
Article
The aim of this study was to further characterize the memory-enhancing profile of S 18986 a positive allosteric modulator of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors. S 18986 was studied in two mouse models of age-related memory deficits, using radial maze paradigms involving long-term/declarative mem...
Article
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, expe...
Article
The potential memory-enhancing properties of two dopamine agonists currently used in patients with Parkinson's disease, piribedil (1, 10 mg/kg/day, subcutaneously) and bromocriptine (5 mg/kg/day, subcutaneously), were evaluated in three experiments. Although piribedil (10 mg/kg) and bromocriptine equally enhanced spontaneous object recognition in y...
Article
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In 2005, 84% of Wayana Amerindians living in the upper marshes of the Maroni River in French Guiana presented a hair mercury concentration exceeding the limit set up by the World Health Organization (10 microg/g). To determine whether this mercurial contamination was harmful, mice have been fed diets prepared by incorporation of mercury-polluted fi...
Article
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An increasing body of evidence indicates that the vitamin A metabolite retinoic acid (RA) plays a role in adult brain plasticity by activating gene transcription through nuclear receptors. Our previous studies in mice have shown that a moderate downregulation of retinoid-mediated transcription contributed to aging-related deficits in hippocampal lo...
Article
Accumulating evidence suggest that alterations in Reelin-mediated signaling may contribute to neuronal dysfunction associated with Alzheimer's disease (AD), the most common form of senile dementia. However, limited information is available on the effect of age, the major risk factor of AD, on Reelin expression. Here, we report that normal aging in...
Article
The hypothesis that hippocampal activity at encoding is causally related to subsequent declarative memory expression is tested in the mouse, by using lidocaine inactivation of the hippocampus in combination with c-fos neuroimaging analysis. We employed a two-stage radial maze paradigm of spatial discrimination, which was previously shown to dissoci...
Article
Full-text available
Ample data indicate that tone and contextual fear conditioning differentially require the amygdala and the hippocampus. However, mechanisms subserving the adaptive selection among environmental stimuli (discrete tone vs context) of those that best predict an aversive event are still elusive. Because the hippocampal cholinergic neurotransmission is...
Article
A large number of studies have investigated the effects of chronic ethanol administration (CEA) on performance in different types of learning and memory tasks in adult rodents. As a general rule, CEA has been reported to impair performance, although this depends both on the condition of administration (e.g. duration, presence or not of a withdrawn...
Article
Vitamin A and its derivatives, the retinoids, have recently been reported to be implicated in the synaptic plasticity of the hippocampus and in cognitive functions. Acting via transcription factors, retinoids can regulate gene expression via their nuclear receptors [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)]. We recently showed...
Article
To what extent the hippocampus is required for contextual conditioning remains a matter of debate. The present experiments examined the effects of ibotenate hippocampal lesions on discriminative fear conditioning to context in mice using measures of freezing in two conditioning paradigms. In both paradigms animals received foot shock as the uncondi...
Article
A two-stage radial arm maze (RAM) task has been designed recently to demonstrate a specific age-related memory deficit in mice. It highlights the contrast between normal and deficient memory expression in a spatial discrimination problem depending on how to-be discriminated arms were presented to the animal. This specific deficit has been interpret...
Article
The effects of ibotenate hippocampal lesions on discrimination performance in an eight-arm radial maze were investigated in mice, using a three-stage paradigm in which the only parameter that varied among stages was the way the arms were presented. In the initial learning phase (stage 1), animals learned the valence or reward contingency associated...
Article
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...
Article
Full-text available
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]. I...
Article
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 infer...
Article
Full-text available
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 (baite...
Article
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 (baite...
Article
Full-text available
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 w...
Article
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 -independe...
Article
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).
Article
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...
Article
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 a...
Article
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...
Article
The concept of central cholinergic intervention in learning and memory processes has been largely derived from pharmacological studies and has been reinforced by more recent research into dementing cognitive disorders (Bartus et al., 1982). Systemic pharmacological treatments, however, globally affect central cholinergic neurones so that little res...
Article
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-maz...