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Elvira de Leonibus"How the brain adjusts to an increasing number of objects to remember ? "

Abstract :

How much information can we remember for a short time interval?
This is a question that has been discussed for many years. In the 1956, George A. Miller was perhaps the first to suggest that humans are only able to hold seven, plus or minus two digits, of information in a short retention time interval; this limit is generally called memory span. In our lab we are investigating how the brain copes to an increasing number of objects. To this aim, we developed a behavioral procedure to study object memory load in mice, and showed that mice, similarly to humans and primates, have a limited object memory span that is impaired by hippocampus damage. We then demonstrated that GluR1 AMPA-R phosphorylation increased within the hippocampus immediately after the exposure to high memory load but not to low memory load, suggesting that GluR1 AMPA-R phosphorylation confers plasticity and supports memory maintenance. This process is controlled by the activation of the N-Methyl-D-Aspartate (NMDA)-calcium-calmodulin-dependent-kinases (CaMK) II-protein-kinase A (PKA) pathways. The activation of the same pathways also controls long-term memory formation in high memory load condition, by promoting new protein synthesis. This suggests that the NMDA-CaMKII-PKA pathways exert a bidirectional control over both short and long term memory, by activating AMPA receptor phosphorylation and new protein synthesis, respectively. These results have important heuristic and clinical implications as they open new perspectives on the understanding of the role of the hippocampus in item memory, the molecular mechanisms underlying the regulation of short-term memory and its relationship with long term memory in high memory load conditions. This work was supported by a grant from Alzheimer's Association -NIRG-10-173992 to EDL.

Selected publications

1.    Sannino S*, Russo F, Perri V, Torromino G, Fragapane P, Mele A, De Leonibus E. How the hippocampus regulates working memory load in mice. Under review

2.    Rinaldi A , Minicocci E, Cifra A, Dompietro A, Oliverio A, De Leonibus E, Mele A. Place memory: more inside the specific contribution of the hippocampus and the dorsal striatum. Submitted

3.    Rotundo IL, Faraso S, De Leonibus E, Nigro G, Vitiello C, Lancioni A, Di Napoli D., Castaldo S, Russo V, Russo F, Piluso S, Auricchio A, Nigro V. Worsening of cardiomyopathy using Deflazacort in an animal model rescued by gene therapy. Plos One 2011, 6.

4. Lodato S*, Tomassy GS*, De Leonibus E*, Yoryani GU, Andolfi G, Armentano M., Gaztelu JM, Arlotta P, Mendez de la Prida L, Studer M. Loss of COUP-TF1 function alters the balance of CGE- and MGE-derived interneurons resulting in an epilepsy resistant phenotype. Journal Neuroscience 2011 31(12):4650-62

5.    De Leonibus E*, Costantini VJA*, Massaro A, Vanni V, Mandolesi G, Luvisetto S, Pavone F, Oliverio A, Mele A. Cognitive and neural determinants of response strategy in the dual- solution plusmaze task. Learning & Memory 2011, 18(4):241-4.

6.    Spampanato C*, De Leonibus E*, Dama P, Gargiulo A, Fraldi A, Sorrentino CN, Russo F, Nusco E, Auricchio A, Surace EM, Ballabio A. Efficacy of a combined intracerebral and systemic gene delivery approach for the treatment of a severe lysosomal storage disorder. Human Molecular Genetics 2010 19(5):860-9.

Srubek Tomassy G*, De Leonibus E*, Jabaudon D*, Lodato S, Alfano C. Mele A, Macklis JD, Studer M. Area-Specific temporal control of corticospinal motor neuron differentiation by COUP-TF1. PNAS (2009-11792)

Scientific focus :

My general research interest is to understanding the neurobiology of learning and memory processes, both in normal and pathological conditions. Memory has been divided into different categories, according to a temporal gradient (short term vs long term memory) and a qualitative distinction (explicit and implicit memory) of long-term memory. These psychological constructs are believed to subtend different and parallel neural circuits, different biological processes and different genetic determinants. In particular the hippocampus is generally believed to mediate explicit long-term memory formation and maintenance, but not implicit long-term memory or working memory. On the contrary, fronto-striatal circuits are believed to support both working memory and implicit long-term memory.
The focus of my research is to understand the neurobiology or fronto-striatal memory functions and its relationship with medial temporal lobe activity, and in particular to investigate:
• The inter-hemispheric neuronal and functional connections between the medial temporal lobe regions and the different striatal subregions;
• The interaction between second-messenger molecular cascades activated by dopamine and glutamate receptors within the striatum, in neurodegenerative disorders;
• The neurobiology of working memory capacity, which is the number of elements that can be retained in memory for seconds to minutes.
For these aims neurochemical, pharmacological, histochemical, and behavioural genetic approaches will be used. Understanding the neurobiology of memory is a first necessary step to treat cognitive symptoms in neurodegenerative disorders, such as ageing, Parkinson’ and Alzheimer disease, which is the ultimate goal of my research.

Pauline Lafenêtre du Laboratoire NutriNeuro.