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Restorative Plasticity At Corticostriatal Excitatory Synapses

Restorative Plasticity At Corticostriatal Excitatory Synapses

Objective

Long-lasting, activity-dependent synaptic changes are thought to underlie the ability of the brain to translate experiences into memories and seem to represent the cellular model underlying learning and memory processes. Alteration of brain plasticity may lead to the motor and cognitive disturbances observed in neurodegenerative diseases. Therapeutic approaches targeting synaptic plasticity could prevent neuronal degeneration and restore altered motor and cognitive functions. Long-term synaptic plasticity, long-term potentiation and long-term depression, are widely expressed at excitatory synapses throughout the brain and have both been described at corticostriatal connections, at which they might underlie motor-skill learning, cognitive performance and reward mechanisms. Unique feature of corticostriatal plasticity is the observation that the loss of these opposite forms of synaptic plasticity has been observed in experimental models of neurodegenerative disorders such as Parkinson’s disease (PD). REPLACES will use cortical striatal plasticity and its alterations in experimental PD to explore basic mechanisms of brain plasticity and repair and to translate the new generated knowledge into novel restorative therapeutic approaches. The long-term efficacy of new treatments for PD will be conditioned by their ability to restore, structurally and functionally, the synaptic wiring of striatal neurons and physiological synaptic plasticity. REPLACES addresses the potential restorative effects of either novel pharmacological treatments or neuronal transplants on the corticostriatal microcircuitry. Since chronic treatment with DA precursor L-DOPA induces in the majority of PD patients a maladaptative plasticity causing dyskinesia, innovative strategies should prevent the development of this disabling condition. REPLACES will characterize corticostriatal synaptic plasticity from molecular aspects to clinical neurophysiology involving behavioural and morphological analysis.

Coordinator

UNIVERSITA DEGLI STUDI DI MILANO

Address

Via Festa Del Perdono 7
20122 Milano

Italy

Activity type

Higher or Secondary Education Establishments

EU Contribution

€ 619 957,49

Administrative Contact

Monica Di Luca (Prof.)

Participants (11)

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FONDAZIONE SANTA LUCIA

Italy

EU Contribution

€ 498 001

LEIBNIZ-INSTITUT FUER NEUROBIOLOGIE

Germany

EU Contribution

€ 377 785

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE

France

EU Contribution

€ 407 294

CARDIFF UNIVERSITY

United Kingdom

EU Contribution

€ 400 830

LUNDS UNIVERSITET

Sweden

EU Contribution

€ 500 052

FUNDACION PARA LA INVESTIGACION MEDICA APLICADA FIMA

Spain

EU Contribution

€ 344 380

UNIVERSITY COLLEGE LONDON

United Kingdom

EU Contribution

€ 370 146

CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE CNRS

France

EU Contribution

€ 376 745

ASSOCIATION EUROPEENNE POUR LA MALADIE DE PARKINSON

Belgium

EU Contribution

€ 80 000

CFc srl

Italy

EU Contribution

€ 160 000

XIGEN SA

Switzerland

EU Contribution

€ 84 575,51

Project information

Grant agreement ID: 222918

Status

Closed project

  • Start date

    1 November 2008

  • End date

    30 April 2013

Funded under:

FP7-HEALTH

  • Overall budget:

    € 5 454 740,41

  • EU contribution

    € 4 219 766

Coordinated by:

UNIVERSITA DEGLI STUDI DI MILANO

Italy