Memory, Aging and Plasticity (MAP)

 

Research themes

 

 

Mechanisms of memory reconsolidation - Pascal Roullet

We will study the influence of strength of the initial learning experience, keeping in mind the possibility of the existence of an information processing continuum that extends from synaptic consolidation to systemic consolidation, via synaptic reconsolidation. During initial consolidation and reconsolidation the mechanisms involved are in part common, with a protein synthetic phase. We will attempt to identify the newly synthesized proteins using a large scale transcriptomic approach based on the detection of changes in the expression of genes of interest with cerebral plasticity. In addition, following studies demonstrating the blockade of the reconsolidation of an aversive memory in animals using propranolol, a clinical study in patients suffering from Post-Traumatic Stress Disorder (PTSD) has shown that a low dose of propranolol administered during a single reactivation session reduces the conditioned emotional response associated with the memory trace in question. However, the mode of action of this treatment is not known. We will investigate whether propranolol acts uniquely on memories associated with a stressful event, or on any kind of memory, and we will attempt to identify the brain region (or regions) involved.

 

Functional role of hippocampal neurogenesis in memory processes - Claire Rampon

We have recently shown that new neurons of the dentate gyrus are recruited into hippocampal neuronal circuits that allow the recall of spatial memory, and that their activation depends upon learning conditions. Additionally, our data indicate that the recruitment of new neurons contributes to the updating and reinforcement of a previously acquired memory. In order to test this hypothesis, we will develop an experimental procedure that will allow us to vary the strength of the initial learning experience in a spatial navigation protocol, in order to estimate the extent to which the recruitment of new neurons during recall depends on the strength of learning (number of trials). Subsequent studies using expression of immediate-early genes should allow us to study the possible reorganization of hippocampocortical network after systemic consolidation of spatial memory.

Newborn cell in the dentate gyrus of an adult mouse (GFP labelling)

(Zerwas, unpublished)

 

 

Synaptic plasticity induced in the hippocampal CA3 region by contextual learning - Lionel Dahan et Jean-Michel Lassalle

In line with the work carried out in the laboratory on the role of different hippocampal regions in the formation of a contextual memory, we will study synaptic plasticity induced in the CA3 region of the hippocampus during contextual learning from a new angle, by direct electrophysiological observation of LTP in behaving mice, in order to answer 3 questions: What pathways afferent to CA3 are potentiated during this learning? What is the time course of this potentiation? Is it reinforced during consolidation?

 

Synaptic plasticity induced by Place Preference Conditioning - Bernard Frances

We study the involvement of protein degradation by the proteasome pathway in the establishment of the reinforcing effects of morphine in the mouse. The consequences of the localized infusion of specific inhibitors of the proteasome into the brain will be studied in various paradigms in which the motivational effects of the drug are or are not associated with prior learning. These behavioral tests will be completed by 1) a study of the fate of morphine target proteins and of Post-Synaptic Density proteins as a function of the level of inhibition of the proteasome during the different phases of place preference conditioning (acquisition, consolidation, reinstatement), 2) a study of the role of the new neurons produced by the adult hippocampus, and 3) a study of synaptic plasticity (LTP or LTD) measured by recording field potentials following the stimulation of structures afferent to the Nucleus Accumbens in freely behaving mice.

© Groupe de recherche sur l'alcool et les pharmacodépendances, Université de Picardie Jules Verne

Place preference conditioning to morphine: Injections of morphine are associated with a particular compartment during conditioning (acquisition). During the recall phase, 24h after conditioning, the mouse spends more time in the compartment associated with morphine, in spite of the absence of an injection. This behavior becomes extinct in around 3 weeks. The injection of a very low dose of morphine is sufficient for the mouse to again spend more time in the compartment previously associated with the drug (reinstatement).

 

 

Impact of stress and of various factors affecting neuronal plasticity on physiological and pathological aging

 

Three aspects of the positive effects of moderate stress on aging will be studied in
Drosophila :

1. Since exposure to cold increases resistance to fungi, we will investigate whether an immunodeficient mutant of the Toll pathway can be protected against infection by moderate stress, and whether this stress is sufficient to activate the Toll pathway and lead to the accumulation of antifungal peptides in the hemolymph, thus conferring resistance to infection.
2. The effects of moderate stress at different ages. Our previous work has been carried out with young flies, but it would be even more interesting to show that moderate stress has positive effects at an advanced age, for example on resistance to strong stress such as heat or infection.
3. Effects of food restriction combined with a moderate stress on aging. We showed recently that the suppression of an important source of protein increases the lifespan of flies at least of mated. It would be interesting to know if this positive effect can be added to the positive effects of exposure to moderate stress.

 

Moreover, we are investigating the existence of a link between the modulation of adult neurogenesis and cognitive deficits in Alzheimer’s disease (AD), using mouse models of this disease. In particular, we will study the long-term impact of environmental enrichment – a functional recovery technique – on the accumulation of soluble (toxic) and aggregated forms of the amyloid beta peptide and the activation of hippocampocortical networks during cognitive processes (immediate-early gene mapping techniques). We will evaluate whether the beneficial effects of enrichment are associated with a stimulation of neurogenesis. This work will be combined with a multifactorial study of limiting factors in the production of new neurons in AD, based on ex vivo experiments using a combination of electrophysiological patch-clamp recording and multiplex single-cell RT-PCR. This multidisciplinary approach, which has not as yet been taken with mice, will allow us to correlate the electrical and pharmacological properties of an individual cell with an analysis of its transcriptome.